Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Vanpouille-Box, C. et al. Trial watch: immune checkpoint blockers for cancer therapy. Oncoimmunology 6, e1373237 (2017).
Khalil, D. N., Smith, E. L., Brentjens, R. J. & Wolchok, J. D. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat. Rev. Clin. Oncol. 13, 273–290 (2016).
Gotwals, P. et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat. Rev. Cancer 17, 286–301 (2017).
Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541–550 (2018).
Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321–330 (2017).
Fridman, W. H., Zitvogel, L., Sautes-Fridman, C. & Kroemer, G. The immune contexture in cancer prognosis and treatment. Nat. Rev. Clin. Oncol. 14, 717–734 (2017).
Woo, S. R. et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41, 830–842 (2014).
Deng, L. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843–852 (2014).
Gao, P. et al. Cyclic [G(2′,5′)pA(3′,5′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell 153, 1094–1107 (2013).
Diner, E. J. et al. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep. 3, 1355–1361 (2013).
Ablasser, A. et al. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498, 380–384 (2013).
Zhang, X. et al. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51, 226–235 (2013).
Gao, P. et al. Structure–function analysis of STING activation by c[G(2′,5′)pA(3′,5′)p] and targeting by antiviral DMXAA. Cell 154, 748–762 (2013).
Chen, Q., Sun, L. & Chen, Z. J. Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142–1149 (2016).
Corrales, L., McWhirter, S. M., Dubensky, T. W. Jr & Gajewski, T. F. The host STING pathway at the interface of cancer and immunity. J. Clin. Invest. 126, 2404–2411 (2016).
Wang, H. et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc. Natl Acad. Sci. USA 114, 1637–1642 (2017).
Ishikawa, H., Ma, Z. & Barber, G. N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788–792 (2009).
Corrales, L. et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11, 1018–1030 (2015).
Demaria, O. et al. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity. Proc. Natl Acad. Sci. USA 112, 15408–15413 (2015).
Ohkuri, T. et al. Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site. Cancer Immunol. Immunother. 66, 705–716 (2017).
Curran, E. et al. STING pathway activation stimulates potent immunity against acute myeloid leukemia. Cell Rep. 15, 2357–2366 (2016).
Fu, J. et al. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci. Transl. Med. 7, 283ra252 (2015).
Dubensky, T. W. Jr., Kanne, D. B. & Leong, M. L. Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants. Ther. Adv. Vaccines 1, 131–143 (2013).
Koshy, S. T., Cheung, A. S., Gu, L., Graveline, A. R. & Mooney, D. J. Liposomal delivery enhances immune activation by STING agonists for cancer immunotherapy. Adv. Biosyst. 1, 1600013 (2017).
Hanson, M. C. et al. Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants. J. Clin. Invest. 125, 2532–2546 (2015).
Mullard, A. Can innate immune system targets turn up the heat on ‘cold’ tumours? Nat. Rev. Drug Discov. 17, 3–5 (2018).
Vrignaud, S., Benoit, J. P. & Saulnier, P. Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles. Biomaterials 32, 8593–8604 (2011).
Manganiello, M. J., Cheng, C., Convertine, A. J., Bryers, J. D. & Stayton, P. S. Diblock copolymers with tunable pH transitions for gene delivery. Biomaterials 33, 2301–2309 (2012).
Wilson, J. T. et al. Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles. AAPS. J. 17, 358–369 (2014).
O’Neil, C. P., Suzuki, T., Demurtas, D., Finka, A. & Hubbell, J. A. A novel method for the encapsulation of biomolecules into polymersomes via direct hydration. Langmuir 25, 9025–9029 (2009).
Kilchrist, K. V., Evans, B. C., Brophy, C. M. & Duvall, C. L. Mechanism of enhanced cellular uptake and cytosolic retention of MK2 inhibitory peptide nano-polyplexes. Cell Mol. Bioeng. 9, 368–381 (2016).
Nelson, C. E. et al. Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances endosome escape, stability, blood circulation time, and bioactivity in vivo. ACS Nano 7, 8870–8880 (2013).
Discher, D. E. & Ahmed, F. Polymersomes. Annu. Rev. Biomed. Eng. 8, 323–341 (2006).
Jain, S. & Bates, F. S. Consequences of nonergodicity in aqueous binary PEO–PB micellar dispersions. Macromolecules 2004, 1511–1523 (2004).
Mai, Y. & Eisenberg, A. Self-assembly of block copolymers. Chem. Soc. Rev. 41, 5969–5985 (2012).
Parker, B. S., Rautela, J. & Hertzog, P. J. Antitumour actions of interferons: implications for cancer therapy. Nat. Rev. Cancer 16, 131–144 (2016).
Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15, 541–555 (2014).
Wilson, D. R. et al. Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy. Nanomedicine 14, 237–246 (2018).
Harlin, H. et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 69, 3077–3085 (2009).
Munn, D. H. & Mellor, A. L. The tumor-draining lymph node as an immune-privileged site. Immunol. Rev. 213, 146–158 (2006).
Reddy, S. T., Rehor, A., Schmoekel, H. G., Hubbell, J. A. & Swartz, M. A. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. J. Control. Release 112, 26–34 (2006).
Reddy, S. T. et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol. 25, 1159–1164 (2007).
Lizotte, P. H. et al. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat. Nanotechnol. 11, 295–303 (2016).
Mantovani, A., Cassatella, M. A., Costantini, C. & Jaillon, S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 11, 519–531 (2011).
Liang, H. et al. Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. Nat. Commun. 8, 1736 (2017).
Shi, L. et al. PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor. Clin. Cancer Res. 22, 1173–1184 (2016).
Ries, C. H. et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 25, 846–859 (2014).
Rudqvist, N. P. et al. Radiotherapy and CTLA-4 blockade shape the TCR repertoire of tumor-infiltrating T cells. Cancer Immunol. Res. 6, 139–150 (2018).
Murthy, V., Minehart, J. & Sterman, D. H. Local immunotherapy of cancer: innovative approaches to harnessing tumor-specific immune responses. J. Natl Cancer Inst. 109, djx097 (2017).
Overwijk, W. W. et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J. Exp. Med. 198, 569–580 (2003).
Moynihan, K. D. et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat. Med. 22, 1402–1410 (2016).
Ghosh, S., Basu, S. & Thayumanavan, S. Simultaneous and reversible functionalization of copolymers for biological applications. Macromolecules 2006, 5595–5597 (2006).
Matini, T. et al. Synthesis and characterization of variable conformation pH responsive block co-polymers for nucleic acid delivery and targeted cell entry. Polym. Chem. 5, 1626–1636 (2014).
Gaffney, B. L., Veliath, E., Zhao, J. & Jones, R. A. One-flask synthesis of c-di-GMP and the [Rp,Rp] and [Rp,Sp] thiophosphate analogues. Org. Lett. 12, 3269–3271 (2010).