Turning Cold into Hot: Firing up the Tumor Microenvironment

Binnewies, 2018, Understanding the tumor immune microenvironment (TIME) for effective therapy, Nat. Med., 24, 541, 10.1038/s41591-018-0014-x Balkwill, 2001, Inflammation and cancer: back to Virchow?, Lancet, 357, 539, 10.1016/S0140-6736(00)04046-0 Vitale, 2019, Macrophages and metabolism in the tumor microenvironment, Cell Metab., 30, 36, 10.1016/j.cmet.2019.06.001 Scharping, 2016, Tumor microenvironment metabolism: a new checkpoint for anti-tumor immunity, Vaccines (Basel), 4, E46, 10.3390/vaccines4040046 Reina-Campos, 2017, Metabolism shapes the tumor microenvironment, Curr. Opin. Cell Biol., 48, 47, 10.1016/j.ceb.2017.05.006 Finicle, 2018, Nutrient scavenging in cancer, Nat. Rev. Cancer, 18, 619, 10.1038/s41568-018-0048-x Vijayan, 2017, Targeting immunosuppressive adenosine in cancer, Nat. Rev. Cancer, 17, 709, 10.1038/nrc.2017.86 Giraldo, 2014, The immune contexture of primary and metastatic human tumours, Curr. Opin. Immunol., 27, 8, 10.1016/j.coi.2014.01.001 Fridman, 2012, The immune contexture in human tumours: impact on clinical outcome, Nat. Rev. Cancer, 12, 298, 10.1038/nrc3245 Bindea, 2013, Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer, Immunity, 39, 782, 10.1016/j.immuni.2013.10.003 Gajewski, 2015, The next hurdle in cancer immunotherapy: overcoming the non-T-cell-inflamed tumor microenvironment, Semin. Oncol., 42, 663, 10.1053/j.seminoncol.2015.05.011 Zemek, 2019, Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment, Sci. Transl. Med., 11, 10.1126/scitranslmed.aav7816 Liu, 2020, Targeting innate sensing in the tumor microenvironment to improve immunotherapy, Cell. Mol. Immunol., 17, 13, 10.1038/s41423-019-0341-y Quail, 2017, The microenvironmental landscape of brain tumors, Cancer Cell, 31, 326, 10.1016/j.ccell.2017.02.009 Zeng, 2013, Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas, Int. J. Radiat. Oncol. Biol. Phys., 86, 343, 10.1016/j.ijrobp.2012.12.025 Pyonteck, 2013, CSF-1R inhibition alters macrophage polarization and blocks glioma progression, Nat. Med., 19, 1264, 10.1038/nm.3337 Vom Berg, 2013, Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection, J. Exp. Med., 210, 2803, 10.1084/jem.20130678 Hildner, 2008, Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity, Science, 322, 1097, 10.1126/science.1164206 Spranger, 2017, Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy, Cancer Cell, 31, 711, 10.1016/j.ccell.2017.04.003 Dangaj, 2019, Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors, Cancer Cell, 35, 885, 10.1016/j.ccell.2019.05.004 Botelho, 2019, Combination of Synthetic Long Peptides and XCL1 fusion proteins results in superior tumor control, Front. Immunol., 10, 294, 10.3389/fimmu.2019.00294 Chow, 2019, Intratumoral activity of the CXCR3 chemokine system is required for the efficacy of anti-PD-1 therapy, Immunity, 50, 1498, 10.1016/j.immuni.2019.04.010 Garris, 2018, Successful anti-PD-1 Cancer Immunotherapy Requires T cell-dendritic cell crosstalk involving the cytokines IFN-gamma and IL-12, Immunity, 49, 1148, 10.1016/j.immuni.2018.09.024 Li, 2013, Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects, Science, 341, 1390, 10.1126/science.1244040 Li, 2018, The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer, J. Exp. Med., 215, 1287, 10.1084/jem.20180139 Deng, 2014, STING-Dependent Cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors, Immunity, 41, 843, 10.1016/j.immuni.2014.10.019 Woo, 2014, STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors, Immunity, 41, 830, 10.1016/j.immuni.2014.10.017 Corrales, 2015, Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity, Cell Rep., 11, 1018, 10.1016/j.celrep.2015.04.031 Demaria, 2015, STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity, Proc. Natl. Acad. Sci. U. S. A., 112, 15408, 10.1073/pnas.1512832112 Schadt, 2019, Cancer-cell-intrinsic cGAS expression mediates tumor immunogenicity, Cell Rep., 29, 1236, 10.1016/j.celrep.2019.09.065 Yang, 2019, STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade, J. Clin. Invest., 130, 4350, 10.1172/JCI125413 Reislander, 2019, BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors, Nat. Commun., 10, 3143, 10.1038/s41467-019-11048-5 Heijink, 2019, BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity, Nat. Commun., 10, 100, 10.1038/s41467-018-07927-y Pantelidou, 2019, PARP inhibitor efficacy depends on CD8(+) T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer, Cancer Discov., 9, 722, 10.1158/2159-8290.CD-18-1218 Ishizuka, 2019, Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade, Nature, 565, 43, 10.1038/s41586-018-0768-9 Wellenstein, 2018, Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape, Immunity, 48, 399, 10.1016/j.immuni.2018.03.004 Spranger, 2018, Impact of oncogenic pathways on evasion of antitumour immune responses, Nat. Rev. Cancer, 18, 139, 10.1038/nrc.2017.117 Spranger, 2015, Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity, Nature, 523, 231, 10.1038/nature14404 Cheng, 2019, Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle, Nat. Immunol., 20, 206, 10.1038/s41590-018-0290-0 Ho, 2014, Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNgamma, Cancer Res., 74, 3205, 10.1158/0008-5472.CAN-13-3461 Goel, 2017, CDK4/6 inhibition triggers anti-tumour immunity, Nature, 548, 471, 10.1038/nature23465 Schaer, 2018, 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, 10.1016/j.celrep.2018.02.053 Pavlova, 2016, The emerging hallmarks of cancer metabolism, Cell Metab., 23, 27, 10.1016/j.cmet.2015.12.006 Zhang, 2018, Metabolic control of CD8(+) T cell fate decisions and antitumor immunity, Trends Mol. Med., 24, 30, 10.1016/j.molmed.2017.11.005 Marijt, 2019, Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFNgamma receptor signaling, J. Immunother. Cancer, 7, 152, 10.1186/s40425-019-0627-8 Ramakrishnan, 2014, Oxidized lipids block antigen cross-presentation by dendritic cells in cancer, J. Immunol., 192, 2920, 10.4049/jimmunol.1302801 Ziegler, 2018, Mitophagy in intestinal epithelial cells triggers adaptive immunity during tumorigenesis, Cell, 174, 88, 10.1016/j.cell.2018.05.028 Osorio, 2014, The unfolded-protein-response sensor IRE-1alpha regulates the function of CD8alpha+ dendritic cells, Nat. Immunol., 15, 248, 10.1038/ni.2808 Cubillos-Ruiz, 2015, ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis, Cell, 161, 1527, 10.1016/j.cell.2015.05.025 Cao, 2019, ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression, Nat. Commun., 10, 1280, 10.1038/s41467-019-09263-1 Hurst, 2019, Endoplasmic reticulum stress contributes to mitochondrial exhaustion of CD8(+) T cells, Cancer Immunol. Res., 7, 476, 10.1158/2326-6066.CIR-18-0182 Scharping, 2016, The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction, Immunity, 45, 374, 10.1016/j.immuni.2016.07.009 Siska, 2017, Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma, JCI Insight, 2, 10.1172/jci.insight.93411 Dumauthioz, 2020, Enforced PGC-1alpha expression promotes CD8 T cell fitness, memory formation and antitumor immunity, Cell. Mol. Immunol., 10.1038/s41423-020-0365-3 Zheng, 2019, Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance, Nat. Immunol., 20, 1656, 10.1038/s41590-019-0511-1 Gropper, 2017, Culturing CTLs under hypoxic conditions enhances their cytolysis and improves their anti-tumor function, Cell Rep., 20, 2547, 10.1016/j.celrep.2017.08.071 Wang, 2019, CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy, Nature, 569, 270, 10.1038/s41586-019-1170-y Sheng, 2018, LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade, Cell, 174, 549, 10.1016/j.cell.2018.05.052 Peng, 2015, Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy, Nature, 527, 249, 10.1038/nature15520 Luo, 2018, DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer, Nat. Commun., 9, 248, 10.1038/s41467-017-02630-w DuPage, 2015, The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation, Immunity, 42, 227, 10.1016/j.immuni.2015.01.007 Wang, 2018, Targeting EZH2 reprograms intratumoral regulatory T cells to enhance cancer immunity, Cell Rep., 23, 3262, 10.1016/j.celrep.2018.05.050 Huang, 2019, EZH2 inhibitor GSK126 suppresses antitumor immunity by driving production of myeloid-derived suppressor cells, Cancer Res., 79, 2009, 10.1158/0008-5472.CAN-18-2395 Pascual-Garcia, 2019, LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8(+) T cell tumor-infiltration impairing anti-PD1 therapy, Nat. Commun., 10, 2416, 10.1038/s41467-019-10369-9 Li, 2019, In vivo epigenetic CRISPR screen identifies Asf1a as an immunotherapeutic target in Kras-mutant lung adenocarcinoma, Cancer Discov. Youngblood, 2017, Effector CD8 T cells dedifferentiate into long-lived memory cells, Nature, 552, 404, 10.1038/nature25144 Scott-Browne, 2016, Dynamic changes in chromatin accessibility occur in CD8(+) T cells responding to viral infection, Immunity, 45, 1327, 10.1016/j.immuni.2016.10.028 Ghoneim, 2017, De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation, Cell, 170, 142, 10.1016/j.cell.2017.06.007 Zhang, 2016, Mammalian target of rapamycin complex 2 controls CD8 T cell memory differentiation in a Foxo1-dependent manner, Cell Rep., 14, 1206, 10.1016/j.celrep.2015.12.095 He, 2017, Ezh2 phosphorylation state determines its capacity to maintain CD8(+) T memory precursors for antitumor immunity, Nat. Commun., 8, 2125, 10.1038/s41467-017-02187-8 Philip, 2017, Chromatin states define tumour-specific T cell dysfunction and reprogramming, Nature, 545, 452, 10.1038/nature22367 Wang, 2019, TOX promotes the exhaustion of antitumor CD8(+) T cells by preventing PD1 degradation in hepatocellular carcinoma, J. Hepatol., 71, 731, 10.1016/j.jhep.2019.05.015 Scott, 2019, TOX is a critical regulator of tumour-specific T cell differentiation, Nature, 571, 270, 10.1038/s41586-019-1324-y Kim, 2019, VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers, Sci. Immunol., 10.1126/sciimmunol.aay0555 Khan, 2019, TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion, Nature, 571, 211, 10.1038/s41586-019-1325-x Alfei, 2019, TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection, Nature, 571, 265, 10.1038/s41586-019-1326-9 Achard, 2018, Lighting a fire in the tumor microenvironment using oncolytic immunotherapy, EBioMedicine, 31, 17, 10.1016/j.ebiom.2018.04.020 Chon, 2019, Tumor microenvironment remodeling by intratumoral oncolytic vaccinia virus enhances the efficacy of immune-checkpoint blockade, Clin. Cancer Res., 25, 1612, 10.1158/1078-0432.CCR-18-1932 Walsh, 2019, Endogenous T cells prevent tumor immune escape following adoptive T cell therapy, J. Clin. Invest., 129, 5400, 10.1172/JCI126199 Walsh, 2019, Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity, J. Clin. Invest., 129, 518, 10.1172/JCI121004 Giesen, 2014, Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry, Nat. Methods, 11, 417, 10.1038/nmeth.2869 Tirosh, 2016, Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq, Science, 352, 189, 10.1126/science.aad0501 Azizi, 2018, Single-cell map of diverse immune phenotypes in the breast tumor microenvironment, Cell, 174, 1293, 10.1016/j.cell.2018.05.060 Savas, 2018, Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis, Nat. Med., 24, 986, 10.1038/s41591-018-0078-7 Wagner, 2019, A single-cell atlas of the tumor and immune ecosystem of human breast cancer, Cell, 177, 1330, 10.1016/j.cell.2019.03.005 Zhang, 2019, Deep single-cell RNA sequencing data of individual T cells from treatment-naive colorectal cancer patients, Sci. Data, 6, 131, 10.1038/s41597-019-0131-5 Zheng, 2017, Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing, Cell, 169, 1342, 10.1016/j.cell.2017.05.035 Chevrier, 2017, An immune atlas of clear cell renal cell carcinoma, Cell, 169, 736, 10.1016/j.cell.2017.04.016 Guo, 2018, Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing, Nat. Med., 24, 978, 10.1038/s41591-018-0045-3 Lambrechts, 2018, Phenotype molding of stromal cells in the lung tumor microenvironment, Nat. Med., 24, 1277, 10.1038/s41591-018-0096-5 Puram, 2017, Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer, Cell, 171, 1611, 10.1016/j.cell.2017.10.044 Pott, 2015, Single-cell ATAC-seq: strength in numbers, Genome Biol., 16, 172, 10.1186/s13059-015-0737-7 Cusanovich, 2015, Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing, Science, 348, 910, 10.1126/science.aab1601 Buenrostro, 2015, Single-cell chromatin accessibility reveals principles of regulatory variation, Nature, 523, 486, 10.1038/nature14590 Macosko, 2015, Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets, Cell, 161, 1202, 10.1016/j.cell.2015.05.002 Duncan, 2019, Advances in mass spectrometry based single-cell metabolomics, Analyst, 144, 782, 10.1039/C8AN01581C Paget, 1989, The distribution of secondary growths in cancer of the breast. 1889, Cancer Metastasis Rev., 8, 98 Zhu, 2019, Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors, J. Immunother. Cancer, 7, 265, 10.1186/s40425-019-0755-1 Chang, 2015, Metabolic competition in the tumor microenvironment is a driver of cancer progression, Cell, 162, 1229, 10.1016/j.cell.2015.08.016 Quail, 2017, Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF, Nat. Cell Biol., 19, 974, 10.1038/ncb3578 Neal, 2018, Organoid modeling of the tumor immune microenvironment, Cell, 175, 1972, 10.1016/j.cell.2018.11.021 Dijkstra, 2018, Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids, Cell, 174, 1586, 10.1016/j.cell.2018.07.009 Rosato, 2018, Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models, Breast Cancer Res., 20, 108, 10.1186/s13058-018-1037-4 Morton, 2016, Humanized mouse xenograft models: narrowing the tumor-microenvironment gap, Cancer Res., 76, 6153, 10.1158/0008-5472.CAN-16-1260