Glioblastoma (GBM) is the deadliest form of brain cancer, with a median survival of less than 2 years despite surgical resection, radiation, and chemotherapy. GBM’s rapid progression, resistance to therapy, and inexorable recurrence have been attributed to several factors, including its rapid growth rate, its molecular heterogeneity, its propensity to infiltrate vital brain structures, the regenerative capacity of treatment-resistant cancer stem cells, and challenges in achieving high concentrations of chemotherapeutic agents in the central nervous system. Escape from immunosurveillance is increasingly recognized as a landmark event in cancer biology. Translation of this framework to clinical oncology has positioned immunotherapy as a pillar of cancer treatment. Amid the bourgeoning successes of cancer immunotherapy, GBM has emerged as a model of resistance to immunotherapy. Here we review the mechanisms of immunotherapy resistance in GBM and discuss how insights into GBM–immune system interactions might inform the next generation of immunotherapeutics for GBM and other resistant pathologies.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Nachman, M. W. & Crowell, S. L. Estimate of the mutation rate per nucleotide in humans. Genetics 156, 297–304 (2000).
Vogelstein, B. et al. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319, 525–532 (1988).
Hastings, K. G. et al. Socioeconomic differences in the epidemiologic transition from heart disease to cancer as the leading cause of death in the United States, 2003 to 2015: an observational study. Ann. Intern. Med. 169, 836–844 (2018).
Ribatti, D. The concept of immune surveillance against tumors. The first theories. Oncotarget 8, 7175–7180 (2017).
Dunn, G. P., Old, L. J. & Schreiber, R. D. The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329–360 (2004). This review (ref. 5) describes the interactions between a tumor and the immune system that govern tumor progression or clearance. This framework is important for understanding how tumors respond to immunological pressure.
Gong, J., Chehrazi-Raffle, A., Reddi, S. & Salgia, R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J. Immunother. Cancer 6, 765–2 (2018).
Rizvi, N. A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015). This (ref. 7) was a landmark study highlighting the connection between a tumor’s mutational landscape and response to immune-checkpoint blockade.
Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409–413 (2017).
Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012). This study (ref. 9) demonstrated the clinical activity of PD-1 blockade and established PD-L1 expression on tumor cells as a biomarker of response.
Gibney, G. T., Weiner, L. M. & Atkins, M. B. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 17, e542–e551 (2016).
Zhao, J. et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat. Med. 25, 462–469 (2019).
Sharma, P., Hu-Lieskovan, S., Wargo, J. A. & Ribas, A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168, 707–723 (2017).
Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).
Veglia, F., Perego, M. & Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19, 108–119 (2018).
Jiang, H. et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 22, 851–860 (2016).
Lim, M., Xia, Y., Bettegowda, C. & Weller, M. Current state of immunotherapy for glioblastoma. Nat. Rev. Clin. Oncol. 15, 422–442 (2018).
Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23–34 (2015).
Weller, M. et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 18, 1373–1385 (2017).
Omuro, A. et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-oncol. 20, 674–686 (2018).
Gettinger, S. N. et al. Clinical features and management of acquired resistance to PD-1 axis inhibitors in 26 patients with advanced non-small cell lung cancer. J. Thorac. Oncol. 13, 831–839 (2018).
Comiskey, M. C., Dallos, M. C. & Drake, C. G. Immunotherapy in prostate cancer: teaching an old dog new tricks. Curr. Oncol. Rep. 20, 75 (2018).
Louis, D. N. et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 131, 803–820 (2016).
Ostrom, Q.T., Gittleman, H., Stetson, L., Virk, S.M. & Barnholtz-Sloan, J.S. in Current Understanding and Treatment of Gliomas Vol. 163, pp. 1–14 (Springer International Publishing, 2014).
Stupp, R. et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987–996 (2005). This trial (ref. 24) established the current standard of care for patients with glioblastoma.
Verhaak, R. G. W. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010).
Romo, C. G. et al. Widely metastatic IDH1-mutant glioblastoma with oligodendroglial features and atypical molecular findings: a case report and review of current challenges in molecular diagnostics. Diagn. Pathol. 14, 16 (2019).
Darmanis, S. et al. Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Reports 21, 1399–1410 (2017).
Chen, J. et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488, 522–526 (2012).
Bao, S. et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756–760 (2006).
Cheng, L. et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell 153, 139–152 (2013).
Schäfer, N. et al. Longitudinal heterogeneity in glioblastoma: moving targets in recurrent versus primary tumors. J. Transl. Med. 17, 96 (2019).
Li, A. et al. Surface biotinylation of cytotoxic T lymphocytes for in vivo tracking of tumor immunotherapy in murine models. Cancer Immunol. Immunother. 65, 1545–1554 (2016).
O’Rourke, D. M. et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med. 9, eaaa0984-2 (2017).
Memarnejadian, A. et al. PD-1 blockade promotes epitope spreading in anticancer CD8+ T cell responses by preventing fratricidal death of subdominant clones to relieve immunodomination. J. Immunol. 199, 3348–3359 (2017).
Mathios, D. et al. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM. Sci. Transl. Med. 8, 370ra180 (2016). This study (ref. 35) demonstrated that systemic temozolomide induced immunosuppression that prevented the effectiveness of PD-1 blockade in a preclinical model.
McGranahan, T., Therkelsen, K. E., Ahmad, S. & Nagpal, S. Current state of immunotherapy for treatment of glioblastoma. Curr. Treat. Options Oncol. 20, 24 (2019).
Hung, A. L. et al. TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. OncoImmunology 7, e1466769 (2018).
Kim, J. E. et al. Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas. Clin. Cancer Res. 23, 124–136 (2017).
Zeng, J. et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int. J. Radiat. Oncol. 86, 343–349 (2013). This study (ref. 39) was the first to show activity of PD-1 blockade in a glioma model.
Wu, A. et al. Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of tumor microenvironment. J. Neurooncol. 13, 293 (2019).
Jackson, C. M. & Lim, M. Immunotherapy for glioblastoma: playing chess, not checkers. Clin. Cancer Res. 24, 4059–4061 (2018).
Cloughesy, T. F. et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat. Med. 25, 477–486 (2019).
Schalper, K. A. et al. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat. Med. 25, 470–476 (2019).
Bauer, H.-C., Krizbai, I. A., Bauer, H. & Traweger, A. “You Shall Not Pass”—tight junctions of the blood brain barrier. Front. Neurosci. 8, 392 (2014).
Spector, R. Nutrient transport systems in brain: 40 years of progress. J. Neurochem. 111, 315–320 (2009).
Coureuil, M., Lécuyer, H., Bourdoulous, S. & Nassif, X. A journey into the brain: insight into how bacterial pathogens cross blood-brain barriers. Nat. Rev. Microbiol. 15, 149–159 (2017).
Jackson, C. M., Lim, M. & Drake, C. G. Immunotherapy for brain cancer: recent progress and future promise. Clin. Cancer Res. 20, 3651–3659 (2014).
Hutter, G. et al. Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. Proc. Natl Acad. Sci. USA 116, 997–1006 (2019).
Salter, M. W. & Stevens, B. Microglia emerge as central players in brain disease. Nat. Med. 23, 1018–1027 (2017).
Nimmerjahn, A., Kirchhoff, F. & Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318 (2005).
Tang, Y. & Le, W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53, 1181–1194 (2016).
Ransohoff, R. M. & Cardona, A. E. The myeloid cells of the central nervous system parenchyma. Nature 468, 253–262 (2010).
Brabb, T. et al. In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J. Exp. Med. 192, 871–880 (2000).
Na, S.-Y. et al. Oligodendrocytes enforce immune tolerance of the uninfected brain by purging the peripheral repertoire of autoreactive CD8+ T cells. Immunity 37, 134–146 (2012).
Klein, R. S. et al. IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis. J. Immunol. 172, 550–559 (2004).
Sandrone, S., Moreno-Zambrano, D., Kipnis, J. & van Gijn, J. A. (delayed) history of the brain lymphatic system. Nat. Med. 25, 538–540 (2019).
Cserr, H. F., Harling-Berg, C. J. & Knopf, P. M. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 2, 269–276 (1992).
Laman, J. D. & Weller, R. O. Drainage of cells and soluble antigen from the CNS to regional lymph nodes. J. Neuroimmune Pharmacol. 8, 840–856 (2013).
Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337–341 (2015). This study (ref. 59) described lymphatic channels paralleling the dural venous sinuses as the major route of antigen egress from the CNS.
Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 560, 185–191 (2018).
Da Mesquita, S., Fu, Z. & Kipnis, J. The meningeal lymphatic system: a new player in neurophysiology. Neuron 100, 375–388 (2018).
Han, S. et al. Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in glioma. Br. J. Cancer 110, 2560–2568 (2014).
Bouffet, E. et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J. Clin. Oncol. 34, 2206–2211 (2016).
Mitchell, D. A. et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 519, 366–369 (2015).
Weiss, T., Weller, M., Guckenberger, M., Sentman, C. L. & Roth, P. NKG2D-based CAR T cells and radiotherapy exert synergistic efficacy in glioblastoma. Cancer Res. 78, 1031–1043 (2018).
Tomaszewski, W., Sanchez-Perez, L., Gajewski, T.F. & Sampson, J.H. Brain tumor microenvironment and host state: implications for immunotherapy. Clin. Cancer Res. https://doi.org/10.1158/1078-0432.CCR-18-1627 (2019).
Jackson, C. M. et al. Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clin. Cancer Res. 22, 1161–1172 (2016). This study (ref. 67) showed that tumor location is an independent mediator of systemic immunosuppression through multiple mechanisms, including deletion and tolerance of tumor antigen-directed T cells.
Chongsathidkiet, P. et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat. Med. 24, 1459–1468 (2018). This study (ref. 68) addressed the long-standing question of how GBMs induce lymphopenia by demonstrating that T cells are sequestered in the bone marrow of patients with GBM and animals with brain tumors of other pathologies.
Patel, A. P. et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344, 1396–1401 (2014).
McLendon, R. et al. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).
Qazi, M. A. et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann. Oncol. 28, 1448–1456 (2017).
Wang, Q. et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 32, 42–56.e6 (2017).
Sottoriva, A. et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc. Natl Acad. Sci. USA 110, 4009–4014 (2013).
McGranahan, N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351, 1463–1469 (2016). This study (ref. 74) found that high-quality clonal neoantigens are critical for response to immune checkpoint blockade.
Łuksza, M. et al. A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature 551, 517–520 (2017).
Balachandran, V. P. et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551, 512–516 (2017).
Brennan, C. W. et al. The somatic genomic landscape of glioblastoma. Cell 155, 462–477 (2013).
Sampson, J. H. et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 28, 4722–4729 (2010).
Wood, M. D., Reis, G. F., Reuss, D. E. & Phillips, J. J. Protein analysis of glioblastoma primary and posttreatment pairs suggests a mesenchymal shift at recurrence. J. Neuropathol. Exp. Neurol. 75, 925–935 (2016).
Liau, L. M. et al. First results on survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J. Transl. Med. 16, v1–v2 (2018).
Danilova, L. et al. The mutation-associated neoantigen functional expansion of specific T cells (MANAFEST) assay: a sensitive platform for monitoring antitumor immunity. Cancer Immunol. Res. 6, 888–899 (2018).
Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234–239 (2019).
Hilf, N. et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature 565, 240–245 (2019).
Desjardins, A. et al. Recurrent glioblastoma treated with recombinant poliovirus. N. Engl. J. Med. 379, 150–161 (2018).
Lang, F. F. et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J. Clin. Oncol. 36, 1419–1427 (2018).
Cloughesy, T. F. et al. Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro-oncol. 20, 1383–1392 (2018).
Brown, M. C. et al. Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen–specific CTLs. Sci. Transl. Med. 9, eaan4220-2 (2017). This study (ref. 87) demonstrated that treatment with an oncolytic poliovirus reprograms DCs, releases damage- or pathogen-associated molecular patterns, and generates sustained cytotoxic responses.
Grossman, S. A. et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin. Cancer Res. 17, 5473–5480 (2011).
Maxwell, R. et al. Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system. OncoImmunology 7, e1500108 (2018).
Giles, A. J. et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J. Immunother. Cancer 6, 235–232 (2018).
Topalian, S. L., Drake, C. G. & Pardoll, D. M. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27, 450–461 (2015).
Garcia-Diaz, A. et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Reports 19, 1189–1201 (2017).
Koyama, S. et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun. 7, 10501 (2016).
Woroniecka, K. et al. T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma. Clin. Cancer Res. 24, 4175–4186 (2018). This study (ref. 94) delineates mechanisms of adaptive resistance in glioblastoma and describes a severe state of exhaustion among tumor-infiltrating T cells.
Bauer, C. et al. Prevailing over T cell exhaustion: New developments in the immunotherapy of pancreatic cancer. Cancer Lett. 381, 259–268 (2016).
Johanns, T. M. et al. Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade immunotherapy. Cancer Discov. 6, 1230–1236 (2016).
Chen, Z. & Hambardzumyan, D. Immune microenvironment in glioblastoma subtypes. Front. Immunol. 9, 1004 (2018).
Mantovani, A., Marchesi, F., Malesci, A., Laghi, L. & Allavena, P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 14, 399–416 (2017).
Takenaka, M. C. et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat. Neurosci. 22, 729–740 (2019).
Engler, J. R. et al. Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas. PLoS One 7, e43339 (2012).
Naeini, K. M. et al. Identifying the mesenchymal molecular subtype of glioblastoma using quantitative volumetric analysis of anatomic magnetic resonance images. Neuro Oncol. 15, 626–634 (2013).
Pagès, F. et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 391, 2128–2139 (2018).
Zhu, X., Fujita, M., Snyder, L. A. & Okada, H. Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J. Neurooncol. 104, 83–92 (2011).
Elmore, M. R. P. et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82, 380–397 (2014).
Pyonteck, S. M. et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 19, 1264–1272 (2013).
Quail, D. F. et al. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352, aad3018 (2016).
Butowski, N. et al. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro Oncol. 18, 557–564 (2016).
Trinchieri, G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3, 133–146 (2003).
Wang, Y. et al. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment. Biomaterials 112, 153–163 (2017).
Zhu, H. et al. Surgical debulking promotes recruitment of macrophages and triggers glioblastoma phagocytosis in combination with CD47 blocking immunotherapy. Oncotarget 8, 12145–12157 (2017).
Zhang, M. et al. Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS One 11, e0153550–e0153552 (2016).
Feng, M. et al. Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc. Natl Acad. Sci. USA 112, 2145–2150 (2015).
Sosa, R. A., Murphey, C., Ji, N., Cardona, A. E. & Forsthuber, T. G. The kinetics of myelin antigen uptake by myeloid cells in the central nervous system during experimental autoimmune encephalomyelitis. J. Immunol. 191, 5848–5857 (2013).
Karman, J., Ling, C., Sandor, M. & Fabry, Z. Initiation of immune responses in brain is promoted by local dendritic cells. J. Immunol. 173, 2353–2361 (2004).
Ursu, R. et al. Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma-A phase II multicentric, randomised study. Eur. J. Cancer 73, 30–37 (2017).
Carpentier, A. et al. Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. Neuro-oncol. 12, 401–408 (2010).
Garzon-Muvdi, T. et al. Dendritic cell activation enhances anti-PD-1 mediated immunotherapy against glioblastoma. Oncotarget 9, 20681–20697 (2018).
Anagnostou, V. et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 7, 264–276 (2017).
Rosenthal, R. et al. The TRACERx consortium et al. Neoantigen-directed immune escape in lung cancer evolution. Nature 567, 479–485 (2019).
Verdegaal, E. M. E. et al. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature 536, 91–95 (2016).
M.L. receives research support from Arbor, Aegenus, Altor, Accuray, and DNAtrix and serves as a consultant for Tocagen, SQZ Technologies, Bristol–Myers Squibb, Stryker, and Baxter.
Peer review information Zoltan Fehervari was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Jackson, C.M., Choi, J. & Lim, M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat Immunol 20, 1100–1109 (2019). https://doi.org/10.1038/s41590-019-0433-y
Journal of Experimental & Clinical Cancer Research (2021)
Acta Neuropathologica Communications (2021)
Biomarker Research (2021)
Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: a mechanistic review
Cancer Cell International (2021)
Signal Transduction and Targeted Therapy (2021)