Immunotherapy has revolutionized the treatment of patients with cancer. However, promoting antitumour immunity in patients with tumours that are resistant to these therapies remains a challenge. Thermal therapies provide a promising immune-adjuvant strategy for use with immunotherapy, mostly owing to the capacity to reprogramme the tumour microenvironment through induction of immunogenic cell death, which also promotes the recruitment of endogenous immune cells. Thus, thermal immunotherapeutic strategies for various cancers are an area of considerable research interest. In this Review, we describe the role of the various thermal therapies and provide an update on attempts to combine these with immunotherapies in clinical trials. We also provide an overview of the preclinical development of various thermal immuno-nanomedicines, which are capable of combining thermal therapies with various immunotherapy strategies in a single therapeutic platform. Finally, we discuss the challenges associated with the clinical translation of thermal immuno-nanomedicines and emphasize the importance of multidisciplinary and inter-professional collaboration to facilitate the optimal translation of this technology from bench to bedside.
Immunotherapy has revolutionized cancer therapy, and the clinical effectiveness of approaches such as immune-checkpoint inhibitors and cellular immunotherapies has created substantial improvements in outcomes.
Thermal therapies designed to deliver local hyperthermia can promote antitumour immunity via the induction of immunogenic cell death following tumour ablation and by reprogramming the tumour microenvironment.
Several early-phase trials combining thermal therapies with immunotherapy are either ongoing or completed, and some have provided encouraging results that support the further clinical development of combined thermal therapy–immunotherapy approaches.
Thermal immuno-nanomedicines are thermal therapies that also incorporate immunotherapies within a single nanoparticle, potentially enabling simultaneous activity and synergy between these two modalities.
Preclinical evidence suggests that thermal immuno-nanomedicines provide a promising cancer therapeutic strategy; however, coordinated efforts from multidisciplinary teams of experts will be required to drive the clinical translation of this technology.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Smartphone-based platforms implementing microfluidic detection with image-based artificial intelligence
Nature Communications Open Access 11 March 2023
Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy
Nano-Micro Letters Open Access 08 February 2023
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 per month
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Nam, J. et al. Cancer nanomedicine for combination cancer immunotherapy. Nat. Rev. Mater. 4, 398–414 (2019).
Pearlman, A. H. et al. Targeting public neoantigens for cancer immunotherapy. Nat. Cancer 2, 487–497 (2021).
Li, Y. et al. Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy. Nat. Commun. 12, 951 (2021).
Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020).
Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).
Singh, A. K. & McGuirk, J. P. CAR T cells: continuation in a revolution of immunotherapy. Lancet Oncol. 21, E168–E178 (2020).
Vitale, I., Shema, E., Loi, S. & Galluzzi, L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat. Med. 27, 212–224 (2021).
Newman, J. H. et al. Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. Proc. Natl Acad. Sci. USA 117, 1119–1128 (2020).
Jackson, C. M., Choi, J. & Lim, M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat. Immunol. 20, 1100–1109 (2019).
Bonaventura, P. et al. Cold tumors: a therapeutic challenge for immunotherapy. Front. Immunol. 10, 168 (2019).
Certo, M., Tsai, C. H., Pucino, V., Ho, P. C. & Mauro, C. Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat. Rev. Immunol. 21, 151–161 (2021).
Chen, Y., McAndrews, K. M. & Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 18, 792–804 (2021).
Rodriguez Garcia, A. et al. CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat. Commun. 12, 877 (2021).
Schmid, P. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21, 44–59 (2020).
Adams, S. et al. Atezolizumab plus nab-paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up a phase 1b clinical trial. JAMA Oncol. 5, 334–342 (2019).
Esperanza Rodriguez Ruiz, M., Vitale, I., Harrington, K. J., Melero, I. & Galluzzi, L. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat. Immunol. 21, 120–134 (2020).
Patel, R. B. et al. Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade. Sci. Transl. Med. 13, eabb3631 (2021).
Chang, M., Hou, Z., Wang, M., Li, C. & Lin, J. Recent advances in hyperthermia therapy-based synergistic immunotherapy. Adv. Mater. 33, 2004788 (2021).
Cortes, J. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396, 1817–1828 (2020).
Schmid, P. et al. Pembrolizumab for early triple-negative breast cancer. N. Engl. J. Med. 382, 810–821 (2020).
Liu, W. et al. Combination of immune checkpoint inhibitors with chemotherapy in lung cancer. OncoTargets Ther. 13, 7229–7241 (2020).
Larroquette, M. et al. Combining immune checkpoint inhibitors with chemotherapy in advanced solid tumours: a review. Eur. J. Cancer 158, 47–62 (2021).
Zhou, J. L., Huang, Q., Huang, Z. J. & Li, J. Q. Combining immunotherapy and radiotherapy in lung cancer: a promising future? J. Thorac. Dis. 12, 4498–4503 (2020).
Shirvalilou, S. et al. Magnetic hyperthermia as an adjuvant cancer therapy in combination with radiotherapy versus radiotherapy alone for recurrent/progressive glioblastoma: a systematic review. J. Neurooncol. 152, 419–428 (2021).
Li, Q. et al. Pre- and post-irradiation mild hyperthermia enabled by NIR-II for sensitizing radiotherapy. Biomaterials 257, 120235 (2020).
Sen, A. et al. Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models. Cancer Res. 71, 3872–3880 (2011).
Mu, C. et al. Chemotherapy sensitizes therapy-resistant cells to mild hyperthermia by suppressing heat shock protein 27 expression in triple-negative breast cancer. Clin. Cancer Res. 24, 4900–4912 (2018).
Klaver, C. E. L. et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol. 4, 761–770 (2019).
Shin, D. H., Melnick, K. F., Tran, D. D. & Ghiaseddin, A. P. In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas. J. Neurooncol. 151, 85–92 (2021).
Napoli, A. et al. Noninvasive therapy for osteoid osteoma: a prospective developmental study with MR imaging-guided high-intensity focused ultrasound. Radiology 285, 186–196 (2017).
Friedman, M. et al. Radiofrequency ablation of cancer. Cardiovasc. Interv. Radiol. 27, 427–434 (2004).
Jiang, Y., Huang, J., Xu, C. & Pu, K. Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer. Nat. Commun. 12, 742 (2021).
Fite, B. Z. et al. Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer. Sci. Rep. 11, 927 (2021).
Pan, J. et al. Combined magnetic hyperthermia and Immune therapy for primary and metastatic tumor treatments. ACS Nano 14, 1033–1044 (2020).
Lerner, E. C., Edwards, R. M., Wilkinson, D. S. & Fecci, P. E. Laser ablation: heating up the anti-tumor response in the intracranial compartment. Adv. Drug Deliv. Rev. 185, 114311 (2022).
Pan, Y., Liu, L., Rao, L. & Chen, X. Nanomaterial-mediated ablation therapy for cancer stem cells. Matter 5, 1367–1390 (2022).
Pan, J., Xu, Y., Wu, Q., Hu, P. & Shi, J. Mild magnetic hyperthermia-activated innate immunity for liver cancer therapy. J. Am. Chem. Soc. 143, 8116–8128 (2021).
Chen, Q. et al. Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat. Immunol. 7, 1299–1308 (2006).
Shi, L. et al. Thermal ablation plus toripalimab in patients with advanced hepatocellular carcinoma: phase I results from a multicenter, open-label, controlled phase I/II trial (IR11330). Ann. Oncol. 32, S826–S826 (2021).
Lyu, N. et al. Ablation reboots the response in advanced hepatocellular carcinoma with stable or atypical response during PD-1 therapy: a proof-of-concept study. Front. Oncol. 10, 580241 (2020).
Duffy, A. G. et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J. Hepatol. 66, 545–551 (2017).
Xie, C. et al. Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer. Hepatology 69, 2048–2060 (2019).
Zuo, S. et al. Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what? Theranostics 11, 7471–7487 (2021).
Bailey, S. R. & Maus, M. V. Gene editing for immune cell therapies. Nat. Biotechnol. 37, 1425–1434 (2019).
Fierro, J. et al. Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization. Sci. Rep. 12, 2417 (2022).
Shi, L. et al. CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes. Gene 636, 36–41 (2017).
Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 7, 13193 (2016).
Huang, L. et al. Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy. Nat. Commun. 10, 4871 (2019).
Saccomandi, P., Lapergola, A., Longo, F., Schena, E. & Quero, G. Thermal ablation of pancreatic cancer: a systematic literature review of clinical practice and pre-clinical studies. Int. J. Hyperth. 35, 398–418 (2019).
Chu, K. F. & Dupuy, D. E. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat. Rev. Cancer 14, 199–208 (2014).
van Solinge, T. S., Nieland, L., Chiocca, E. A. & Broekman, M. L. D. Advances in local therapy for glioblastoma — taking the fight to the tumour. Nat. Rev. Neurol. 18, 221–236 (2022).
Elming, P. B. et al. Hyperthermia: the optimal treatment to overcome radiation resistant hypoxia. Cancers 11, 60 (2019).
Issels, R. D. et al. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma. JAMA Oncol. 4, 483–492 (2018).
Krawczyk, P. M. et al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. Proc. Natl Acad. Sci. USA 108, 9851–9856 (2011).
Bailey, C. W. & Sydnor, M. K. Current state of tumor ablation therapies. Dig. Dis. Sci. 64, 951–958 (2019).
Belyanchikov, M. A. et al. Dielectric ordering of water molecules arranged in a dipolar lattice. Nat. Commun. 11, 3927 (2020).
Kok, H. P. et al. Heating technology for malignant tumors: a review. Int. J. Hyperth. 37, 711–741 (2020).
Gao, D. et al. NIR/MRI-guided oxygen-independent carrier-free anti-tumor nano-theranostics. Small 18, 2106000 (2021).
Gao, D. et al. Multifunctional phototheranostic nanomedicine for cancer imaging and treatment. Mater. Today Bio 5, 100035 (2020).
Gao, D. et al. Targeting hypoxic tumors with hybrid nanobullets for oxygen-independent synergistic photothermal and thermodynamic therapy. Nanomicro. Lett. 13, 99 (2021).
Hammill, C. W. et al. Evaluation of a minimally invasive image-guided surgery system for hepatic ablation procedures. Surg. Innov. 21, 419–426 (2014).
Patel, P., Patel, N. V. & Danish, S. F. Intracranial MR-guided laser-induced thermal therapy: single-center experience with the Visualase thermal therapy system. J. Neurosurg. 125, 853–860 (2016).
Mohammadi, A. M. & Schroeder, J. L. Laser interstitial thermal therapy in treatment of brain tumors — the NeuroBlate system. Expert Rev. Med. Devices 11, 109–119 (2014).
Sloan, A. E. et al. Results of the neuroblate system first-in-humans phase I clinical trial for recurrent glioblastoma. J. Neurosurg. 118, 1202–1219 (2013).
Li, X. S., Lovell, J. F., Yoon, J. & Chen, X. Y. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol. 17, 657–674 (2020).
Xia, Y. et al. Long-term effects of repeat hepatectomy vs percutaneous radiofrequency ablation among patients with recurrent hepatocellular carcinoma. JAMA Oncol. 6, 255–263 (2020).
Kinoshita, T. RFA experiences, indications and clinical outcomes. Int. J. Clin. Oncol. 24, 603–607 (2019).
Al Zubaidi, M., Lotter, K., Marshall, M. & Lozinskiy, M. Radiofrequency ablation for renal tumours: a retrospective study from a tertiary centre. Asian J. Urol. 9, 2214–3882 (2021).
Wan, J. & Wang, J. Current progression of radiofrequency ablation (RFA) in clinical application of lung cancer therapy. J. Biomater. Tissue Eng. 9, 417–426 (2019).
Vietti Violi, N. et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol. Hepatol. 3, 317–325 (2018).
Schirmang, T. C. & Dupuy, D. E. Image-guided thermal ablation of nonresectable hepatic tumors using the Cool-Tip radiofrequency ablation system. Expert Rev. Med. Devices 4, 803–814 (2007).
Gaffke, G. et al. Use of semiflexible applicators for radiofrequency ablation of liver tumors. Cardiovasc. Interv. Radiol. 29, 270–275 (2006).
Solmi, L., Nigro, G. & Roda, E. Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle electrode in hepatocellular carcinoma. World J. Gastroenterol. 12, 1098–1104 (2006).
Mohkam, K. et al. No-touch multibipolar radiofrequency ablation vs. surgical resection for solitary hepatocellular carcinoma ranging from 2 to 5 cm. J. Hepatol. 68, 1172–1180 (2018).
King, J. et al. Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer. Br. J. Surg. 91, 217–223 (2004).
Sommer, C. M. et al. CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma: Specific technical aspects and clinical results. Cardiovasc. Interv. Radiol. 36, 731–737 (2013).
Wells, C. D., Kim, H. J., Moirano, M. M., Fleischer, D. E. & Sharma, V. K. Successful ablation of Barrett esophagus (BE) with dysplasia using the Halo360 ablation system: a single-center experience. Am. J. Gastroenterol. 101, S535–S535 (2006).
Rothstein, R. I., Chang, K. J., Overholt, B. F., Bergman, J. J. & Shaheen, N. J. Focal ablation for treatment of dysplastic and non-dysplastic barrett esophagus: safety profile and initial experience with the Halo90 device in 508 cases. Gastrointest. Endosc. 65, AB147–AB147 (2007).
Shen, R. et al. Ultrasonography-guided radiofrequency ablation combined with lauromacrogol sclerotherapy for mixed thyroid nodules. Am. J. Transl. Res. 13, 5035–5042 (2021).
Mayer, T. et al. Spinal metastases treated with bipolar radiofrequency ablation with increased (>70°C) target temperature: pain management and local tumor control. Diagn. Interv. Imaging 102, 27–34 (2021).
Lorenc, T., Kocon, H. & Golebiowski, M. Computed tomography-guided percutaneous radiofrequency and laser ablation for the treatment of osteoid osteoma — long-term follow-up from 5 to 10 years. Pol. J. Radiol. 86, E19–E30 (2021).
Osaki, Y. et al. Clinical effectiveness of bipolar radiofrequency ablation for small liver cancers. J. Gastroenterol. 48, 874–883 (2013).
Llovet, J. M. et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 18, 293–313 (2021).
Yu, M. et al. Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells. Cell. Mol. Immunol. 18, 2153–2164 (2021).
Vogl, T. J. et al. A comparison between 915 MHz and 2450 MHz microwave ablation systems for the treatment of small diameter lung metastases. Diagn. Interv. Radiol. 24, 31–37 (2018).
Livraghi, T., Meloni, F., Solbiati, L. & Zanus, G. Complications of microwave ablation for liver tumors: results of a multicenter study. Cardiovasc. Interv. Radiol. 35, 868–874 (2012).
Imajo, K. et al. New microwave ablation system for unresectable liver tumors that forms large, spherical ablation zones. J. Gastroenterol. Hepatol. 33, 2007–2014 (2018).
Alexander, E. S. et al. Microwave ablation of focal hepatic malignancies regardless of size: a 9-year retrospective study of 64 patients. Eur. J. Radiol. 84, 1083–1090 (2015).
Habert, P. et al. Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice. Int. J. Hyperth. 38, 1140–1148 (2021).
Medhat, E. et al. Value of microwave ablation in treatment of large lesions of hepatocellular carcinoma. J. Dig. Dis. 16, 456–463 (2015).
Filippiadis, D. K. et al. Computed tomography-guided percutaneous microwave ablation of hepatocellular carcinoma in challenging locations: safety and efficacy of high-power microwave platforms. Int. J. Hyperth. 34, 863–869 (2018).
Zhao, H. & Steinke, K. Long-term outcome following microwave ablation of early-stage non-small cell lung cancer. J. Med. Imaging Radiat. Oncol. 64, 787–793 (2020).
Pusceddu, C., Sotgia, B., Fele, R. M. & Melis, L. Treatment of bone metastases with microwave thermal ablation. J. Vasc. Interv. Radiol. 24, 229–233 (2013).
Rostas, J. W., Hong, Y. K., Schulz, B., Sanders, M. E. & Martin, R. C. G. A multi-visceral study comparing three proprietary microwave ablation devices. HPB 19, S158–S159 (2017).
Peek, M. C. L. et al. Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis. Int. J. Hyperth. 33, 191–202 (2017).
Lindner, U. et al. Focal magnetic resonance guided focused ultrasound for prostate cancer: initial North American experience. Can. Urol. Assoc. J. 6, E283–E286 (2012).
Francica, G. Needle track seeding after radiofrequency ablation for hepatocellular carcinoma: prevalence, impact, and management challenge. J. Hepatocell. Carcinoma 4, 23–27 (2017).
Kennedy, J. E. High-intensity focused ultrasound in the treatment of solid tumours. Nat. Rev. Cancer 5, 321–327 (2005).
Rebillard, X. et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer. J. Endourol. 19, 693–701 (2005).
Aliaev, I. et al. Treatment of prostatic cancer with high intensity focused ultrasound (HIFU) using Ablatherm device. Urologiia 6, 39–44 (2007).
Burtnyk, M., Hill, T., Cadieux Pitre, H. & Welch, I. Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup. J. Urol. 193, 1669–1675 (2015).
Meng, Y., Hynynen, K. & Lipsman, N. Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nat. Rev. Neurol. 17, 7–22 (2021).
Temple, M. J. et al. Establishing a clinical service for the treatment of osteoid osteoma using magnetic resonance-guided focused ultrasound: overview and guidelines. J. Ther. Ultrasound 4, 16–16 (2016).
Dobrotwir, A. & Pun, E. Clinical 24 month experience of the first MRgFUS Unit for treatment of uterine fibroids in Australia. J. Med. Imaging Radiat. Oncol. 56, 409–416 (2012).
Knuttel, F. M. et al. Early health technology assessment of magnetic resonance-guided high intensity focused ultrasound ablation for the treatment of early-stage breast cancer. J. Ther. Ultrasound 5, 1–10 (2017).
Najafi, A., Fuchs, B. & Binkert, C. A. Mid-term results of MR-guided high-intensity focused ultrasound treatment for relapsing superficial desmoids. Int. J. Hyperth. 36, 537–541 (2019).
Jung, S. E., Cho, S. H., Jang, J. H. & Han, J. Y. High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications. Abdom. Imaging 36, 185–195 (2011).
Zhao, J. et al. The efficacy of a new high intensity focused ultrasound therapy for locally advanced pancreatic cancer. J. Cancer Res. Clin. Oncol. 143, 2105–2111 (2017).
Leslie, T. A. et al. High intensity focused ultrasound in the treatment of small kidney tumours — the Oxford experience. J. Clin. Oncol. 24, 14645–14645 (2006).
Arcot, R. & Polascik, T. J. Does MRI-guided TULSA provide a targeted approach to ablation? Nat. Rev. Urol. 18, 5–6 (2021).
Nair, S. M. et al. Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective phase I study. BJU Int. 127, 544–552 (2021).
Muto, S. et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn. J. Clin. Oncol. 38, 192–199 (2008).
Gilchrist, R. K. et al. Selective inductive heating of lymph nodes. Ann. Surg. 146, 596–606 (1957).
Gavilan, H. et al. Magnetic nanoparticles and clusters for magnetic hyperthermia: optimizing their heat performance and developing combinatorial therapies to tackle cancer. Chem. Soc. Rev. 50, 11614–11667 (2021).
Song, G. et al. Carbon-coated FeCo nanoparticles as sensitive magnetic-particle-imaging tracers with photothermal and magnetothermal properties. Nat. Biomed. Eng. 4, 325–334 (2020).
Liu, X. et al. Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy. Theranostics 10, 3793–3815 (2020).
Lu, C. et al. Engineering of magnetic nanoparticles as magnetic particle imaging tracers. Chem. Soc. Rev. 50, 8102–8146 (2021).
Ho, D., Sun, X. & Sun, S. Monodisperse magnetic nanoparticles for theranostic applications. Acc. Chem. Res. 44, 875–882 (2011).
Maier-Hauff, K. et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J. Neurooncol. 103, 317–324 (2011).
Galluzzi, L., Buque, A., Kepp, O., Zitvogel, L. & Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017).
Garg, A. D. & Agostinis, P. Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol. Rev. 280, 126–148 (2017).
Li, Z., Deng, J., Sun, J. & Ma, Y. Hyperthermia targeting the tumor microenvironment facilitates immune checkpoint inhibitors. Front. Immunol. 11, 595207 (2020).
Krysko, D. V. et al. Immunogenic cell death and DAMPs in cancer therapy. Nat. Rev. Cancer 12, 860–875 (2012).
Munoz, N. M. et al. Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis. Sci. Rep. 12, 14449 (2022).
Guo, D. F. et al. Exosomes from heat-stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL-6. Immunology 154, 132–143 (2018).
Mace, T. A., Zhong, L. W., Kokolus, K. M. & Repasky, E. A. Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia. Int. J. Hyperth. 28, 9–18 (2012).
Chen, T., Guo, J., Han, C., Yang, M. & Cao, X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J. Immunol. 182, 1449–1459 (2009).
Zhao, W. et al. Hyperthermia differentially regulates TLR4 and TLR2-mediated innate immune response. Immunol. Lett. 108, 137–142 (2007).
Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249–1255 (1999).
Ostberg, J. R., Dayanc, B. E., Yuan, M., Oflazoglu, E. & Repasky, E. A. Enhancement of natural killer (NK) cell cytotoxicity by fever-range thermal stress is dependent on NKG2D function and is associated with plasma membrane NKG2D clustering and increased expression of MICA on target cells. J. Leukoc. Biol. 82, 1322–1331 (2007).
Bae, J.-H. et al. Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J. Immunother. 33, 391–401 (2010).
He, K., Liu, P. & Xu, L. X. The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+ T-cell-mediated antitumor memory immune response. Cell Death Dis. 8, e2703 (2017).
Liu, Y. et al. Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory. Immunother 11, 1293–1302 (2019).
Hurwitz, M. D. Hyperthermia and immunotherapy: clinical opportunities. Int. J. Hyperth. 36, 4–9 (2019).
Rittmeyer, A. et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389, 255–265 (2017).
Wang, S. H. et al. Nanoparticle-based medicines in clinical cancer therapy. Nano Today 45, 101512 (2022).
Cortes, J. et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N. Engl. J. Med. 387, 217–226 (2022).
Paz Ares, L. et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med. 379, 2040–2051 (2018).
Yang, Z. et al. Fighting immune cold and reprogramming immunosuppressive tumor microenvironment with red blood cell membrane-camouflaged nanobullets. ACS Nano 14, 17442–17457 (2020).
Chaudhary, N., Weissman, D. & Whitehead, K. A. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).
Saxena, M., van der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 21, 360–378 (2021).
Teijaro, J. R. & Farber, D. L. COVID-19 vaccines: modes of immune activation and future challenges. Nat. Rev. Immunol. 21, 195–197 (2021).
Li, A. W. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. 17, 528–534 (2018).
Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).
Aikins, M. E., Xu, C. & Moon, J. J. Engineered nanoparticles for cancer vaccination and immunotherapy. Acc. Chem. Res. 53, 2094–2105 (2020).
Chen, P. M. et al. Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination. Biomaterials 230, 119629 (2020).
Liu, L. et al. Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles. Nat. Commun. 12, 5726 (2021).
Zhou, J. R., Kroll, A. V., Holay, M., Fang, R. H. & Zhang, L. F. Biomimetic nanotechnology toward personalized vaccines. Adv. Mater. 32, 1901255 (2020).
Liu, W. L. et al. Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells. Nat. Commun. 10, 3199 (2019).
Chen, Q. et al. A hybrid eukaryotic-prokaryotic nanoplatform with photothermal modality for enhanced antitumor vaccination. Adv. Mater. 32, 1908185 (2020).
Wang, T. et al. A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors. Nat. Commun. 9, 1532 (2018).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Kubli, S. P., Berger, T., Araujo, D. V., Siu, L. L. & Mak, T. W. Beyond immune checkpoint blockade: emerging immunological strategies. Nat. Rev. Drug Discov. 20, 899–919 (2021).
Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480–489 (2011).
Lin, D. Y. W. et al. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc. Natl Acad. Sci. USA 105, 3011–3016 (2008).
Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–1736 (1996).
Pallotta, M. T. et al. Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol. 12, 870–878 (2011).
Dong, C. et al. ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409, 97–101 (2001).
Marangoni, F. et al. Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop. Cell 184, 3998–4015 (2021).
Zaidi, N. & Jaffee, E. M. Immunotherapy transforms cancer treatment. J. Clin. Invest. 129, 46–47 (2019).
Wang, Z. et al. Janus nanobullets combine photodynamic therapy and magnetic hyperthermia to potentiate synergetic anti-metastatic immunotherapy. Adv. Sci. 6, 1901690 (2019).
Liu, J. et al. Tumor hypoxia-activated combinatorial nanomedicine triggers systemic antitumor immunity to effectively eradicate advanced breast cancer. Biomaterials 273, 120847 (2021).
Wang, C. et al. Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis. Adv. Mater. 26, 8154–8162 (2014).
Chao, Y. et al. Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy. Nano Lett. 19, 4287–4296 (2019).
Patsoukis, N., Wang, Q., Strauss, L. & Boussiotis Vassiliki, A. Revisiting the PD-1 pathway. Sci. Adv. 6, eabd2712 (2020).
Chen, L. & Han, X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J. Clin. Invest. 125, 3384–3391 (2015).
Li, H., van der Merwe, P. A. & Sivakumar, S. Biomarkers of response to PD-1 pathway blockade. Br. J. Cancer 126, 1663–1675 (2022).
Liu, X. et al. Ferrimagnetic vortex nanoring-mediated mild magnetic hyperthermia imparts potent immunological effect for treating cancer metastasis. ACS Nano 13, 8811–8825 (2019).
Zhang, Y. et al. Native mitochondria-targeting polymeric nanoparticles for mild photothermal therapy rationally potentiated with immune checkpoints blockade to inhibit tumor recurrence and metastasis. Chem. Eng. J. 424, 130171 (2021).
Duan, X., Chan, C. & Lin, W. Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angew. Chem. Int. Ed. 58, 670–680 (2019).
Martins, F. et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat. Rev. Clin. Oncol. 16, 563–580 (2019).
McManus, M. T. & Sharp, P. A. Gene silencing in mammals by small interfering RNAs. Nat. Rev. Genet. 3, 737–747 (2002).
Saha, K. et al. The NIH somatic cell genome editing program. Nature 592, 195–204 (2021).
Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).
Saw, P. E. & Song, E. W. siRNA therapeutics: a clinical reality. Sci. China Life Sci. 63, 485–500 (2020).
Liu, B. et al. Effects of gold nanoprism-assisted human PD-L1 siRNA on both gene down-regulation and photothermal therapy on lung cancer. Acta Biomater. 99, 307–319 (2019).
Sánchez Rivera, F. J. & Jacks, T. Applications of the CRISPR–Cas9 system in cancer biology. Nat. Rev. Cancer 15, 387–393 (2015).
Grunwald, H. A., Weitzel, A. J. & Cooper, K. L. Applications of and considerations for using CRISPR–Cas9-mediated gene conversion systems in rodents. Nat. Protoc. 17, 3–14 (2022).
Strzyz, P. CRISPR–Cas9 wins nobel. Nat. Rev. Mol. Cell Biol. 21, 714–714 (2020).
Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358–378 (2019).
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L. & Gao, G. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target. Ther. 6, 53 (2021).
Ou, X., Ma, Q., Yin, W., Ma, X. & He, Z. CRISPR/Cas9 gene-editing in cancer immunotherapy: promoting the present revolution in cancer therapy and exploring more. Front. Cell Dev. Biol. 9, 674467 (2021).
Gillmore, J. D. et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).
Tang, H. et al. Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy. Adv. Mater. 33, 2006003 (2021).
Logtenberg, M. E. W., Scheeren, F. A. & Schumacher, T. N. The CD47-SIRPα immune checkpoint. Immunity 52, 742–752 (2020).
Sikic, B. I. et al. First-in-human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers. J. Clin. Oncol. 37, 946–953 (2019).
Advani, R. et al. CD47 blockade by Hu5F9-G4 and Rituximab in non-hodgkin’s lymphoma. N. Engl. J. Med. 379, 1711–1721 (2018).
Liu, X. et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat. Med. 21, 1209–1215 (2015).
Zhou, F. et al. Tumor microenvironment-activatable prodrug vesicles for nanoenabled cancer chemoimmunotherapy combining immunogenic cell death induction and CD47 blockade. Adv. Mater. 31, 1805888 (2019).
Cheng, L., Zhang, X., Tang, J., Lv, Q. & Liu, J. Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy. Biomaterials 275, 120964 (2021).
Chang, M. et al. Colorectal tumor microenvironment-activated bio-decomposable and metabolizable Cu2O@CaCO3 nanocomposites for synergistic oncotherapy. Adv. Mater. 32, 2004647 (2020).
Zhang, X. et al. A MXene-based bionic cascaded-enzyme nanoreactor for tumor phototherapy/enzyme dynamic therapy and hypoxia-activated chemotherapy. Nanomicro Lett. 14, 22 (2021).
Puccetti, P. & Grohmann, U. IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-κB activation. Nat. Rev. Immunol. 7, 817–823 (2007).
Mellor, A. L. & Munn, D. H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4, 762–774 (2004).
Patel, C. H., Leone, R. D., Horton, M. R. & Powell, J. D. Targeting metabolism to regulate immune responses in autoimmunity and cancer. Nat. Rev. Drug Discov. 18, 669–688 (2019).
Wang, Y. et al. Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine. Bioact. Mater. 6, 1513–1527 (2021).
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G. & Vacchelli, E. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology 9, 1777625 (2020).
Peng, J. et al. Photosensitizer micelles together with IDO inhibitor enhance cancer photothermal therapy and immunotherapy. Adv. Sci. 5, 1700891 (2018).
Guo, Y. X. et al. Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy. Biomaterials 276, 121018 (2021).
Jiang, W. et al. Reversing immunosuppression in hypoxic and immune-cold tumors with ultrathin oxygen self-supplementing polymer nanosheets under near infrared light irradiation. Adv. Funct. Mater. 31, 2100354 (2021).
Ren, X. et al. Intelligent nanomedicine approaches using medical gas-mediated multi-therapeutic modalities against cancer. J. Biomed. Nanotechnol. 18, 24–49 (2022).
Kashiwagi, S. et al. Perivascular nitric oxide gradients normalize tumor vasculature. Nat. Med. 14, 255–257 (2008).
Sung, Y. C. et al. Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies. Nat. Nanotechnol. 14, 1160–1169 (2019).
Sadelain, M., Rivière, I. & Riddell, S. Therapeutic T cell engineering. Nature 545, 423–431 (2017).
Perez, C. R. & De Palma, M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10, 5408 (2019).
Weber, E. W., Maus, M. V. & Mackall, C. L. The emerging landscape of immune cell therapies. Cell 181, 46–62 (2020).
Santos, P. M. & Butterfield, L. H. Dendritic cell–based cancer vaccines. J. Immunol. 200, 443–449 (2018).
Lu, J. & Jiang, G. The journey of CAR-T therapy in hematological malignancies. Mol. Cancer 21, 194 (2022).
Zhang, H., Bu, C., Peng, Z., Luo, M. & Li, C. The efficacy and safety of anti-CLL1 based CAR-T cells in children with relapsed or refractory acute myeloid leukemia: a multicenter interim analysis. J. Clin. Oncol. 39, 10000 (2021).
Ying, Z. et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med. 10, 999–1011 (2021).
Piehler, S. et al. Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro. Nanomedicine 28, 102183 (2020).
Beola, L. et al. Dual role of magnetic nanoparticles as intracellular hotspots and extracellular matrix disruptors triggered by magnetic hyperthermia in 3D cell culture models. ACS Appl. Mater. Interfaces 10, 44301–44313 (2018).
Gouarderes, S., Mingotaud, A. F., Vicendo, P. & Gibot, L. Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site. Expert Opin. Drug Deliv. 17, 1703–1726 (2020).
Chen, Q. et al. Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv. Mater. 31, 1900192 (2019).
Ye, Y. et al. A melanin-mediated cancer immunotherapy patch. Sci. Immunol. 2, eaan5692 (2017).
Bear, A. S. et al. Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer. PLoS One 8, e69073 (2013).
Miller, I. C. et al. Enhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control. Nat. Biomed. Eng. 5, 1348–1359 (2021).
Xiong, R. et al. Photothermal nanofibres enable safe engineering of therapeutic cells. Nat. Nanotechnol. 16, 1281–1291 (2021).
Dranoff, G. Cytokines in cancer pathogenesis and cancer therapy. Nat. Rev. Cancer 4, 11–22 (2004).
Briukhovetska, D. et al. Interleukins in cancer: from biology to therapy. Nat. Rev. Cancer 21, 481–499 (2021).
Propper, D. J. & Balkwill, F. R. Harnessing cytokines and chemokines for cancer therapy. Nat. Rev. Clin. Oncol. 19, 237–253 (2022).
Hutmacher, C. & Neri, D. Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory properties for cancer therapy. Adv. Drug Deliv. Rev. 141, 67–91 (2019).
Huang, H., Feng, W., Chen, Y. & Shi, J. Inorganic nanoparticles in clinical trials and translations. Nano Today 35, 100972 (2020).
Liu, Y. et al. Metal-based nanoenhancers for future radiotherapy: radiosensitizing and synergistic effects on tumor cells. Theranostics 8, 1824–1849 (2018).
Tamarkin, L., Myer, L., Haynes, R. & Paciotti, G. CYT-6091 (Aurimune™): a colloidal gold-based tumor-targeted nanomedicine. MRS Proc. 1019, FF01–FF10 (2007).
Teo, P. et al. Complex of TNF-α and modified Fe3O4 nanoparticles suppresses tumor growth by magnetic induction hyperthermia. Cancer Biother. Radiopharm. 32, 379–386 (2017).
Lin, X. et al. Localized NIR-II photo-immunotherapy through the combination of photothermal ablation and in situ generated interleukin-12 cytokine for efficiently eliminating primary and abscopal tumors. Nanoscale 13, 1745–1758 (2021).
Antonio Chiocca, E. Oncolytic viruses. Nat. Rev. Cancer 2, 938–950 (2002).
Kaufman, H. L., Kohlhapp, F. J. & Zloza, A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 14, 642–662 (2015).
Tian, Y., Xie, D. & Yang, L. Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduct. Target. Ther. 7, 117 (2022).
Dolgin, E. Oncolytic viruses get a boost with first FDA-approval recommendation. Nat. Rev. Drug Discov. 14, 369–371 (2015).
Volker, S. A new strategy of cancer immunotherapy combining hyperthermia/oncolytic virus pretreatment with specific autologous anti-tumor vaccination. Cancer Vaccines 2, 1006 (2017).
Chen, R. et al. An analytical solution for temperature distributions in hepatic radiofrequency ablation incorporating the heat-sink effect of large vessels. Phys. Med. Biol. 63, 235026 (2018).
Zhang, X. M. et al. Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and synergistic targeted therapy of residual tumor during HIFU ablation. Biomaterials 35, 5148–5161 (2014).
VanOsdol, J. et al. Sequential HIFU heating and nanobubble encapsulation provide efficient drug penetration from stealth and temperature sensitive liposomes in colon cancer. J. Control. Rel. 247, 55–63 (2017).
Sweeney, E. E., Cano Mejia, J. & Fernandes, R. Photothermal therapy generates a thermal window of immunogenic cell death in neuroblastoma. Small 14, 1800678 (2018).
Nguyen, H. T., Tran, K. K., Sun, B. B. & Shen, H. Activation of inflammasomes by tumor cell death mediated by gold nanoshells. Biomaterials 33, 2197–2205 (2012).
Kokuryo, D., Kumamoto, E. & Kuroda, K. Recent technological advancements in thermometry. Adv. Drug Deliv. Rev. 163, 19–39 (2020).
Saccomandi, P., Schena, E. & Pacella, C. M. in Image-guided Laser Ablation (eds Pacella, C. M., Jiang, T. & Mauri, G.) 145–151 (Springer, 2020).
Zhao, T. R., Desjardins, A. E., Ourselin, S., Vercauteren, T. & Xia, W. F. Minimally invasive photoacoustic imaging: current status and future perspectives. Photoacoustics 16, 100146 (2019).
Goldenberg, S. L., Nir, G. & Salcudean, S. E. A new era: artificial intelligence and machine learning in prostate cancer. Nat. Rev. Urol. 16, 391–403 (2019).
Acosta, J. N., Falcone, G. J., Rajpurkar, P. & Topol, E. J. Multimodal biomedical AI. Nat. Med. 28, 1773–1784 (2022).
Denu, R. A. et al. Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer. Cancer Epidemiol. 40, 7–14 (2016).
Zhou, J., Zeng, Z. & Li, L. A meta-analysis of watson for oncology in clinical application. Sci. Rep. 11, 5792 (2021).
Sindhwani, S. et al. The entry of nanoparticles into solid tumours. Nat. Mater. 19, 566–575 (2020).
de Lazaro, I. & Mooney, D. J. Obstacles and opportunities in a forward vision for cancer nanomedicine. Nat. Mater. 20, 1469–1479 (2021).
Stapleton, S. et al. Radiation and heat improve the delivery and efficacy of nanotherapeutics by modulating intratumoral fluid dynamics. ACS Nano 12, 7583–7600 (2018).
Theek, B. et al. Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. J. Control. Rel. 231, 77–85 (2016).
Golombek, S. K. et al. Tumor targeting via EPR: strategies to enhance patient responses. Adv. Drug Deliv. Rev. 130, 17–38 (2018).
Chauhan, V. P. et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotechnol. 7, 383–388 (2012).
Tong, R. T. et al. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 64, 3731–3736 (2004).
Nel, A., Ruoslahti, E. & Meng, H. New insights into “permeability” as in the enhanced permeability and retention effect of cancer nanotherapeutics. ACS Nano 11, 9567–9569 (2017).
Autio, K. A. et al. Safety and efficacy of BIND-014, a docetaxel nanoparticle targeting prostate-specific membrane antigen for patients with metastatic castration-resistant prostate cancer a phase 2 clinical trial. JAMA Oncol. 4, 1344–1351 (2018).
Wheeler, K. E. et al. Environmental dimensions of the protein corona. Nat. Nanotechnol. 16, 617–629 (2021).
Witwer, K. W. & Wolfram, J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 6, 103–106 (2021).
FDA. 501(k) Premarket Notification 042216 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K042216 (2022).
FDA. Starburst https://fda.report/GUDID/H7877001023300 (2018).
FDA. 501(k) Summary (K140495) https://www.accessdata.fda.gov/cdrh_docs/pdf14/K140495.pdf (2014).
FDA. 501(k) Premarket Notification K073207 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K073207 (2022).
FDA. 510(k) Premarket Notification K093855 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K093855 (2022).
FDA. 510(k) Premarket Notification K093008 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K093008 (2010).
FDA. Letter to Baylis Medical Company Inc re. K161949 https://www.accessdata.fda.gov/cdrh_docs/pdf16/K161949.pdf (2017).
Whooley, S. FDA clears Stryker bone tumor ablation system. Mass Device https://www.massdevice.com/fda-clears-stryker-bone-tumor-ablation/ (2022).
FDA. Letter to Covidien LLC re. K193232 https://www.accessdata.fda.gov/cdrh_docs/pdf19/K193232.pdf (2020).
FDA. 510(k) Premarket Notification K173756 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K173756 (2018).
FDA. 510(k) Premarket Notification K083157 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K083157 (2009).
Microsulis wins FDA approval for upgraded microwave tissue ablation applicator. Medical Device Network https://www.medicaldevice-network.com/uncategorized/newsmicrosulis-wins-fda-approval-for-upgraded-microwave-tissue-ablation-applicator/ (2012).
FDA clears Covidien Ltd evident microwave ablation system for use in nonresectable liver tumor ablation. Biospace https://www.biospace.com/article/releases/fda-clears-covidien-ltd-evident-microwave-ablation-system-for-use-in-nonresectable-liver-tumor-ablation-/ (2008).
FDA. 510(k) Summary Visualase Thermal Therapy System https://www.accessdata.fda.gov/cdrh_docs/pdf8/K081656.pdf (2008).
FDA. Letter to Monteris Medical re K201056 https://www.accessdata.fda.gov/cdrh_docs/pdf20/K201056.pdf (2020).
FDA. 510(k) Premarket Notification K160942 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K160942 (2016).
FDA. 510(k) Premarket Notification K153023 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K153023 (2015).
FDA. Letter to Profound Medical Inc re. K191200 https://www.accessdata.fda.gov/cdrh_docs/pdf19/K191200.pdf (2019).
FDA. Premarket Approval (PMA) P150038 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P150038S006 (2018).
FDA. Recently approved devices h190003 https://www.fda.gov/medical-devices/recently-approved-devices/sonalleve-mr-hifu-h190003 (2020).
Ritchie, R. W. et al. Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up. BJU Int. 106, 1004–1009 (2010).
Zhao, H. et al. Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anticancer Drugs 21, 447–452 (2010).
Onik, G. et al. Abstract 6540: Regression of metastatic cancer and abscopal effects following in situ vaccination by cryosurgical tumor cell lysis and intratumoral immunotherapy: a case series. Cancer Res. 80, 6540–6540 (2020).
X.Z., G.Y. and M.G. acknowledge support from Harvard/MIT. Z.Y. acknowledges research support from the National Natural Science Foundation of China (51703178), China Postdoctoral Science Foundation (2019M663742), Natural Science Foundation of Shaanxi Province (2022JM183), Natural Science Foundation of Zhejiang Province (LWY20H180002), Shaanxi Provincial Key R&D Program (2022SF-342) and Fundamental Research Funds for the Central Universities (xpt012022030, xtr052022012). D.G. acknowledges research support from the National Natural Science Foundation of China (51903203), China Postdoctoral Science Foundation (2019M653661) and Fundamental Research Funds for the Central Universities (xzy012022037). L.J. acknowledges research support from The Program of Innovative Research Team (in Science and Technology) University of Henan Province (23IRTSTHN008) and the Zhongyuan Thousand Talents Plan. Z.T. acknowledges research support from the National Natural Science Foundation of China (82070751).
The authors declare no competing interests.
Peer review information
Nature Reviews Clinical Oncology thanks H. Zhang and the other, anonymous, reviewer(s), for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yang, Z., Gao, D., Zhao, J. et al. Thermal immuno-nanomedicine in cancer. Nat Rev Clin Oncol 20, 116–134 (2023). https://doi.org/10.1038/s41571-022-00717-y
This article is cited by
Smartphone-based platforms implementing microfluidic detection with image-based artificial intelligence
Nature Communications (2023)
Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy
Nano-Micro Letters (2023)