Tumour-intrinsic resistance to immune checkpoint blockade (original) (raw)
Chowell, D. et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science359, 582–587 (2018). ArticleCASPubMed Google Scholar
Pitt, J. M. et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity44, 1255–1269 (2016). ArticleCASPubMed Google Scholar
Fessler, J., Matson, V. & Gajewski, T. F. Exploring the emerging role of the microbiome in cancer immunotherapy. J. Immunother. Cancer7, 108 (2019). ArticlePubMedPubMed Central Google Scholar
Yarchoan, M., Hopkins, A. & Jaffee, E. M. Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med.377, 2500–2501 (2017). ArticlePubMedPubMed Central Google Scholar
Rizvi, N. A. et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science348, 124–128 (2015). Association of mutational burden and sensitivity to immune checkpoint blockade has been observed across malignancies, including lung cancer. This study provides further support for the importance of tumour-intrinsic biology for sensitivity to immune checkpoint blockade. ArticleCASPubMedPubMed Central Google Scholar
van Rooij, N. et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol.31, e439–e442 (2013). ArticlePubMed Google Scholar
Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science344, 641–645 (2014). ArticleCASPubMedPubMed Central Google Scholar
Dighe, A. S., Richards, E., Old, L. J. & Schreiber, R. D. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity1, 447–456 (1994). ArticleCASPubMed Google Scholar
Kaplan, D. H. et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc. Natl Acad. Sci. USA95, 7556–7561 (1998). Dighe et al. (1994) and Kaplan et al. (1998) provide early data indicating the importance of tumour sensitivity to IFNγ in the rejection of tumours by the immune system. ArticleCASPubMedPubMed Central Google Scholar
Manguso, R. T. et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature547, 413–418 (2017). This study uses an in vivo CRISPR screen of the B16 mouse melanoma model treated with anti-PD1 and GVAX. ArticleCASPubMedPubMed Central Google Scholar
Pan, D. et al. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science359, 770–775 (2018). Manguso et al. (2017), Patel et al. (2017) and Pan et al. (2018) describe important CRISPR screens that identify tumour-intrinsic mechanisms of resistance to immunotherapy using in vitro co-culture of B16 mouse melanoma cells and tumour-specific T cells. ArticleCASPubMedPubMed Central Google Scholar
Zaretsky, J. M. et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med.375, 819–829 (2016). This study provides clinical data demonstrating the role of mutations in the interferon signalling pathway (JAK1andJAK2) and antigen presentation (B2M) in acquired resistance to immune checkpoint blockade. ArticleCASPubMedPubMed Central Google Scholar
Gao, J. et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell167, 397–404 (2016). ArticleCASPubMedPubMed Central Google Scholar
Sucker, A. et al. Acquired IFNgamma resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions. Nature communications8, 15440 (2017). ArticleCASPubMedPubMed Central Google Scholar
Wilson, E. B. et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science340, 202–207 (2013). ArticleCASPubMedPubMed Central Google Scholar
Benci, J. L. et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell167, 1540–1554.e12 (2016). ArticleCASPubMedPubMed Central Google Scholar
Kirkwood, J. M. et al. Effect of JAK/STAT or PI3Kδ plus PD-1 inhibition on the tumor microenvironment: Biomarker results from a phase Ib study in patients with advanced solid tumors. Cancer Res.78 (Suppl.), CT176 (2018). Google Scholar
Bach, E. A., Aguet, M. & Schreiber, R. D. The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu. Rev. Immunol.15, 563–591 (1997). ArticleCASPubMed Google Scholar
Paucker, K., Cantell, K. & Henle, W. Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. Virology17, 324–334 (1962). ArticleCASPubMed Google Scholar
Basham, T. Y. & Merigan, T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J. Immunol.130, 1492–1494 (1983). CASPubMed Google Scholar
King, D. P. & Jones, P. P. Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon. J. Immunol.131, 315–318 (1983). CASPubMed Google Scholar
Cole, K. E. et al. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J. Exp. Med.187, 2009–2021 (1998). ArticleCASPubMedPubMed Central Google Scholar
Farber, J. M. A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. Proc. Natl Acad. Sci. USA87, 5238–5242 (1990). ArticleCASPubMedPubMed Central Google Scholar
Luster, A. D., Unkeless, J. C. & Ravetch, J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature315, 672–676 (1985). ArticleCASPubMed Google Scholar
Rodig, S. J. et al. MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci. Transl. Med. 10, (2018). ArticlePubMedCAS Google Scholar
Johnson, D. B. et al. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat. Commun.7, 10582 (2016). ArticleCASPubMedPubMed Central Google Scholar
Johnson, D. B. et al. Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement. JCI Insight.3, (2018).
Shankaran, V. et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature410, 1107–1111 (2001). ArticleCASPubMed Google Scholar
Restifo, N. P. et al. Identification of human cancers deficient in antigen processing. J. Exp. Med.177, 265–272 (1993). The first report of mutations in antigen processing machinery as a mechanism of resistance to immunotherapy in cancer patients. ArticleCASPubMed Google Scholar
D’Urso, C. M. et al. Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. J. Clin. Invest.87, 284–292 (1991). ArticleCASPubMedPubMed Central Google Scholar
Restifo, N. P. et al. Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J. Natl. Cancer Inst.88, 100–108 (1996). ArticleCASPubMed Google Scholar
Sucker, A. et al. Genetic evolution of T-cell resistance in the course of melanoma progression. Clin. Cancer Res.20, 6593–6604 (2014). ArticleCASPubMedPubMed Central Google Scholar
Sade-Feldman, M. et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat. Commun.8, 1136 (2017). ArticlePubMedPubMed CentralCAS Google Scholar
Huang, L. et al. The RNA-binding protein MEX3B mediates resistance to cancer immunotherapy by downregulating HLA-A expression. Clin. Cancer Res.2483, 2017 (2018). Google Scholar
Wellenstein, M. D. & de Visser, K. E. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity48, 399–416 (2018). ArticleCASPubMed Google Scholar
Spranger, S. & Gajewski, T. F. Impact of oncogenic pathways on evasion of antitumour immune responses. Nat. Rev. Cancer18, 139–147 (2018). ArticleCASPubMedPubMed Central Google Scholar
Yaguchi, T. et al. Immune suppression and resistance mediated by constitutive activation of Wnt/beta-catenin signaling in human melanoma cells. J. Immunol.189, 2110–2117 (2012). ArticleCASPubMed Google Scholar
Spranger, S., Bao, R. & Gajewski, T. F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature523, 231–235 (2015). A key article on the role of tumour-intrinsic WNT signalling in immune evasion of cancer. ArticleCASPubMed Google Scholar
Spranger, S., Dai, D., Horton, B. & Gajewski, T. F. Tumor-residing Batf3 dendritic cells are required for effector t cell trafficking and adoptive t cell therapy. Cancer Cell31, 711–723.e714 (2017). ArticleCASPubMedPubMed Central Google Scholar
Holtzhausen, A. et al. Melanoma-derived Wnt5a promotes local dendritic-cell expression of IDO and immunotolerance: opportunities for pharmacologic enhancement of immunotherapy. Cancer Immunol. Res.3, 1082–1095 (2015). ArticleCASPubMedPubMed Central Google Scholar
Zhao, F. et al. Paracrine Wnt5a-beta-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity48, 147–160.e7 (2018). ArticleCASPubMedPubMed Central Google Scholar
Jimenez-Sanchez, A. et al. Heterogeneous tumor-immune microenvironments among differentially growing metastases in an ovarian cancer patient. Cell170, 927–938.e20 (2017). ArticleCASPubMedPubMed Central Google Scholar
Sridharan, V. et al. Immune profiling of adenoid cystic carcinoma: PD-L2 expression and associations with tumor-infiltrating lymphocytes. Cancer Immunol. Res.4, 679–687 (2016). ArticleCASPubMed Google Scholar
Seiwert, T. Y. et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin. Cancer Res.21, 632–641 (2015). ArticleCASPubMed Google Scholar
Sweis, R. F. et al. Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer. Cancer Immunol. Res.4, 563–568 (2016). ArticleCASPubMedPubMed Central Google Scholar
Schaer, D. A. et al. The CDK4/6 inhibitor abemaciclib induces a t cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Rep.22, 2978–2994 (2018). ArticleCASPubMed Google Scholar
Jerby-Arnon, L. et al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell175, 984–997.e24 (2018). In this study, single-cell transcriptomic analysis identifies a CDK4/CDK6-driven signature associated with immune exclusion and poor response to immune checkpoint blockade. ArticleCASPubMedPubMed Central Google Scholar
Deng, J. et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov.8, 216–233 (2018). ArticleCASPubMed Google Scholar
Sumimoto, H., Imabayashi, F., Iwata, T. & Kawakami, Y. The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. J. Exp. Med.203, 1651–1656 (2006). ArticleCASPubMedPubMed Central Google Scholar
Boni, A. et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res.70, 5213–5219 (2010). ArticleCASPubMed Google Scholar
Frederick, D. T. et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin. Cancer Res.19, 1225–1231 (2013). ArticleCASPubMedPubMed Central Google Scholar
Sapkota, B., Hill, C. E. & Pollack, B. P. Vemurafenib enhances MHC induction in BRAF(V600E) homozygous melanoma cells. Oncoimmunology2, e22890 (2013). ArticlePubMedPubMed Central Google Scholar
Acquavella, N. et al. Type I cytokines synergize with oncogene inhibition to induce tumor growth arrest. Cancer Immunol. Res.3, 37–47 (2015). ArticleCASPubMed Google Scholar
Ebert, P. J. R. et al. MAP kinase inhibition promotes t cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity44, 609–621 (2016). ArticleCASPubMed Google Scholar
Hu-Lieskovan, S. et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Sci. Transl. Med.7, 279ra241 (2015). ArticleCAS Google Scholar
Ribas, A. et al. Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma. Nat. Med.25, 936–940 (2019). ArticleCASPubMedPubMed Central Google Scholar
Ascierto, P. A. et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat. Med.25, 941–946 (2019). ArticleCASPubMed Google Scholar
Sullivan, R. J. et al. Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Nat. Med.25, 929–935 (2019). ArticleCASPubMed Google Scholar
Steck, P. A. et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet.15, 356–362 (1997). ArticleCASPubMed Google Scholar
Li, J. et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science275, 1943–1947 (1997). ArticleCASPubMed Google Scholar
Peng, W. et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov.6, 202–216 (2016). ArticleCASPubMed Google Scholar
George, S. et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity46, 197–204 (2017). ArticleCASPubMedPubMed Central Google Scholar
Li, S. et al. The tumor suppressor PTEN has a critical role in antiviral innate immunity. Nat. Immunol.17, 241–249 (2016). ArticleCASPubMed Google Scholar
Sai, J. et al. PI3K inhibition reduces mammary tumor growth and facilitates antitumor immunity and anti-PD1 responses. Clin. Cancer Res.23, 3371–3384 (2017). ArticleCASPubMed Google Scholar
Ali, K. et al. Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature510, 407–411 (2014). ArticleCASPubMedPubMed Central Google Scholar
Castagnoli, L. et al. WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer. Oncogene38, 4047–4060 (2019). ArticleCASPubMedPubMed Central Google Scholar
Paczulla, A. M. et al. Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature572, 254–259 (2019). ArticleCASPubMedPubMed Central Google Scholar
Zhan, T., Rindtorff, N. & Boutros, M. Wnt signaling in cancer. Oncogene36, 1461–1473 (2017). ArticleCASPubMed Google Scholar
Menshawy, A. et al. Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials. Melanoma Res.28, 371–379 (2018). CASPubMed Google Scholar
Dudley, M. E. et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science298, 850–854 (2002). ArticleCASPubMedPubMed Central Google Scholar
Zeng, D. Q. et al. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget7, 13765–13781 (2016). PubMedPubMed Central Google Scholar
Thomas, N. E. et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J. Clin. Oncol.31, 4252–4259 (2013). ArticlePubMedPubMed Central Google Scholar
Galon, J. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science313, 1960–1964 (2006). ArticleCASPubMed Google Scholar
Zhang, L. et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med.348, 203–213 (2003). ArticleCASPubMed Google Scholar
Chen, P. L. et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov.6, 827–837 (2016). ArticlePubMedPubMed CentralCAS Google Scholar
Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature515, 568–571 (2014). This study shows that CD8+T cell density at the invasive margin is predictive of response to anti-PD1 immune checkpoint blockade in patients with melanoma. The presence of tumour-infiltrating T cells is likely to be a biomarker of pre-existing antitumour immune responses in patients who respond to anti-PD1 therapy. ArticleCASPubMedPubMed Central Google Scholar
Le, D. T. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med.372, 2509–2520 (2015). This article suggests that the observation of high response rates to anti-PD1 therapy for tumours with high mutational burden due to mismatch repair deficiency highlights how tumour biology can dictate the response to immune checkpoint blockade. ArticleCASPubMedPubMed Central Google Scholar
Mariathasan, S. et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature554, 544–548 (2018). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Garon, E. B. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med.372, 2018–2028 (2015). ArticlePubMed Google Scholar
Robert, C. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med.372, 320–330 (2015). ArticleCASPubMed Google Scholar
Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol.5, 375–386 (2005). ArticleCASPubMed Google Scholar
Becht, E. et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol.17, 218 (2016). ArticlePubMedPubMed CentralCAS Google Scholar
Ribas, A. et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell170, 1109–1119.e10 (2017). ArticleCASPubMedPubMed Central Google Scholar
Ayers, M. et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Invest.127, 2930–2940 (2017). ArticlePubMedPubMed Central Google Scholar
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G. & Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell160, 48–61 (2015). ArticleCASPubMedPubMed Central Google Scholar
Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell162, 974–986 (2015). ArticleCASPubMedPubMed Central Google Scholar
Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell175, 998–1013.e20 (2018). ArticleCASPubMedPubMed Central Google Scholar
Nishino, M., Ramaiya, N. H., Hatabu, H. & Hodi, F. S. Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat. Rev. Clin. Oncol.14, 655–668 (2017). ArticleCASPubMedPubMed Central Google Scholar
McGranahan, N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science351, 1463–1469 (2016). Using whole-exome sequencing from separate quadrants of a single tumour, McGranahan et al. highlight that clonal neoantigens, rather than subclonal neoantigens, are most closely associated with response to immune checkpoint blockade. ArticleCASPubMedPubMed Central Google Scholar
The problem with neoantigen prediction. Nat. Biotechnol.35, 97, (2017).
Vitiello, A. & Zanetti, M. Neoantigen prediction and the need for validation. Nat. Biotechnol.35, 815–817 (2017). ArticleCASPubMed Google Scholar
Nathanson, T. et al. Somatic mutations and neoepitope homology in melanomas treated with CTLA-4 blockade. Cancer Immunol. Res.5, 84–91 (2017). ArticleCASPubMed Google Scholar
Spranger, S. et al. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. Proc. Natl Acad. Sci. USA.113, E7759–E7768 (2016). ArticleCASPubMedPubMed Central Google Scholar
Cristescu, R. et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science362, (2018). This article shows that tumour mutational burden and pre-existing immune infiltrates provide distinct and complementary pieces of information on potential response to anti-PD1 immune checkpoint blockade.
Wei, S. C., Duffy, C. R. & Allison, J. P. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov.8, 1069–1086 (2018). ArticlePubMed Google Scholar
Redelman-Sidi, G., Glickman, M. S. & Bochner, B. H. The mechanism of action of BCG therapy for bladder cancer–a current perspective. Nat. Rev. Urol.11, 153–162 (2014). ArticleCASPubMed Google Scholar
Kalbasi, A., June, C. H., Haas, N. & Vapiwala, N. Radiation and immunotherapy: a synergistic combination. J. Clin. Invest.123, 2756–2763 (2013). ArticleCASPubMedPubMed Central Google Scholar
Schaue, D. & McBride, W. H. Opportunities and challenges of radiotherapy for treating cancer. Nat. Rev. Clin. Oncol.12, 527–540 (2015). ArticlePubMedPubMed Central Google Scholar
Weichselbaum, R. R., Liang, H., Deng, L. & Fu, Y. X. Radiotherapy and immunotherapy: a beneficial liaison? Nat. Rev. Clin. Oncol.14, 365–379 (2017). ArticleCASPubMed Google Scholar
Demaria, S., Coleman, C. N. & Formenti, S. C. Radiotherapy: changing the game in immunotherapy. Trends cancer2, 286–294 (2016). ArticlePubMedPubMed Central Google Scholar
Kroemer, G., Galluzzi, L., Kepp, O. & Zitvogel, L. Immunogenic cell death in cancer therapy. Annu. Rev. Immunol.31, 51–72 (2013). ArticleCASPubMed Google Scholar
Deng, L. et al. STING-Dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity41, 843–852 (2014). ArticleCASPubMedPubMed Central Google Scholar
Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med.13, 1050–1059 (2007). ArticleCASPubMed Google Scholar
Twyman-Saint Victor, C. et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature520, 373–377 (2015). ArticleCASPubMed Google Scholar
Seifert, L. et al. Radiation therapy induces macrophages to suppress t-cell responses against pancreatic tumors in mice. Gastroenterology150, 1659–1672.e1655 (2016). ArticlePubMed Google Scholar
Patel, S. A. & Minn, A. J. Combination cancer therapy with immune checkpoint blockade: mechanisms and strategies. Immunity48, 417–433 (2018). ArticleCASPubMedPubMed Central Google Scholar
Goldsmith, K., Chen, W., Johnson, D. C. & Hendricks, R. L. Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. J. Exp. Med.187, 341–348 (1998). ArticleCASPubMedPubMed Central Google Scholar
Ribas, A. et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-pd-1 immunotherapy. Cell174, 1031–1032 (2018). ArticleCASPubMed Google Scholar
Ribas, A. et al. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase Ib, multicenter study. Cancer Discov.8, 1250–1257 (2018). ArticleCASPubMedPubMed Central Google Scholar
Guiducci, C., Vicari, A. P., Sangaletti, S., Trinchieri, G. & Colombo, M. P. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res.65, 3437–3446 (2005). ArticleCASPubMed Google Scholar
Vicari, A. P. et al. Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J. Exp. Med.196, 541–549 (2002). ArticleCASPubMedPubMed Central Google Scholar
Wang, H. et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc. Natl Acad. Sci. USA114, 1637–1642 (2017). ArticleCASPubMedPubMed Central Google Scholar
Byrne, K. T. & Vonderheide, R. H. CD40 stimulation obviates innate sensors and drives T cell immunity in cancer. Cell Rep.15, 2719–2732 (2016). ArticleCASPubMedPubMed Central Google Scholar
Kloss, C. C. et al. Dominant-negative TGF-beta receptor enhances PSMA-targeted human car t cell proliferation and augments prostate cancer eradication. Mol. Ther.26, 1855–1866 (2018). ArticleCASPubMedPubMed Central Google Scholar
Roybal, K. T. & Lim, W. A. Synthetic immunology: hacking immune cells to expand their therapeutic capabilities. Annu. Rev. Immunol.35, 229–253 (2017). ArticleCASPubMedPubMed Central Google Scholar
Srivastava, S. et al. Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting. Cancer Cell35, 489–503.e488 (2019). ArticleCASPubMedPubMed Central Google Scholar
Ljunggren, H. G. & Karre, K. In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol. Today11, 237–244 (1990). ArticleCASPubMed Google Scholar
Rezvani, K., Rouce, R., Liu, E. & Shpall, E. Engineering natural killer cells for cancer immunotherapy. Mol. Ther.25, 1769–1781 (2017). ArticleCASPubMedPubMed Central Google Scholar
Andre, P. et al. Anti-NKG2A mAb Is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell175, 1731–1743.e1713 (2018). ArticleCASPubMedPubMed Central Google Scholar