The role of dendritic cells in cancer and anti-tumor immunity

Steinman, 2012, Decisions about dendritic cells: past, present, and future, Annu. Rev. Immunol., 30, 1, 10.1146/annurev-immunol-100311-102839 Anandasabapathy, 2014, Classical Flt3L-dependent dendritic cells control immunity to protein vaccine, J. Exp. Med., 211, 1875, 10.1084/jem.20131397 Nirschl, 2017, IFNγ-dependent tissue-immune homeostasis is Co-opted in the tumor microenvironment, Cell, 170, 10.1016/j.cell.2017.06.016 Baratin, 2015, Homeostatic NF-κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance, Immunity, 42, 627, 10.1016/j.immuni.2015.03.003 Matzinger, 1994, Tolerance, danger, and the extended family, Annu. Rev. Immunol., 12, 991, 10.1146/annurev.iy.12.040194.005015 Galluzzi, 2018, The hallmarks of successful anticancer immunotherapy, Sci. Transl. Med., 10, 10.1126/scitranslmed.aat7807 McGranahan, 2016, Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade, Science, 351, 1463, 10.1126/science.aaf1490 Gajewski, 2017, Cancer immunotherapy targets based on understanding the t cell-inflamed versus non-T cell-inflamed tumor microenvironment, Adv. Exp. Med. Biol., 1036, 19, 10.1007/978-3-319-67577-0_2 Chen, 2017, Elements of cancer immunity and the cancer-immune set point, Nature, 541, 321, 10.1038/nature21349 Garris, 2020, Dendritic cells, the T-cell-inflamed tumor microenvironment, and immunotherapy treatment response, Clin. Cancer Res., 26, 3901, 10.1158/1078-0432.CCR-19-1321 Albert, 1998, Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs, Nature, 392, 86, 10.1038/32183 Nouri-Shirazi, 2000, Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses, J. Immunol., 165, 3797, 10.4049/jimmunol.165.7.3797 Spranger, 2016, Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma, Proc. Natl. Acad. Sci. U. S. A., 113, E7759, 10.1073/pnas.1609376113 Bourdely, 2020, Transcriptional and functional analysis of CD1c(+) human dendritic cells identifies a CD163(+) subset priming CD8(+)CD103(+) t cells, Immunity, 53, 335, 10.1016/j.immuni.2020.06.002 Broz, 2014, Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity, Cancer Cell, 26, 638, 10.1016/j.ccell.2014.09.007 Böttcher, 2018, NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control, Cell, 172, 1022, 10.1016/j.cell.2018.01.004 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 Barry, 2018, A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments, Nat. Med., 24, 1178, 10.1038/s41591-018-0085-8 Mayoux, 2020, Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy, Sci. Transl. Med., 12, 10.1126/scitranslmed.aav7431 Hegde, 2020, Dendritic cell paucity leads to dysfunctional immune surveillance in pancreatic cancer, Cancer Cell, 37, 289, 10.1016/j.ccell.2020.02.008 Lin, 2020, Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis, J. Exp. Med., 217, 10.1084/jem.20190673 de Mingo Pulido, 2018, TIM-3 regulates CD103(+) dendritic cell function and response to chemotherapy in breast cancer, Cancer Cell, 33, 60, 10.1016/j.ccell.2017.11.019 Peng, 2020, PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade, Nat. Commun., 11, 4835, 10.1038/s41467-020-18570-x Oh, 2020, PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer, Nat. Cancer, 1, 681, 10.1038/s43018-020-0075-x Woo, 2014, STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors, Immunity, 41, 830, 10.1016/j.immuni.2014.10.017 Carenza, 2019, Costimulatory molecules and immune checkpoints are differentially expressed on different subsets of dendritic cells, Front. Immunol., 10, 1325, 10.3389/fimmu.2019.01325 Gallois, 2013, Dendritic cell-targeted approaches to modulate immune dysfunction in the tumor microenvironment, Front. Immunol., 4, 436, 10.3389/fimmu.2013.00436 Steinman, 1975, Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen, J. Exp. Med., 141, 804, 10.1084/jem.141.4.804 Steinman, 1973, Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution, J. Exp. Med., 137, 1142, 10.1084/jem.137.5.1142 Steinman, 1974, Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro, J. Exp. Med., 139, 380, 10.1084/jem.139.2.380 Steinman, 1974, Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo, J. Exp. Med., 139, 1431, 10.1084/jem.139.6.1431 Merad, 2013, The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting, Annu. Rev. Immunol., 31, 563, 10.1146/annurev-immunol-020711-074950 Brown, 2019, Transcriptional basis of mouse and human dendritic cell heterogeneity, Cell, 179, 846, 10.1016/j.cell.2019.09.035 Anderson, 2020, Genetic models of human and mouse dendritic cell development and function, Nat. Rev. Immunol. Villani, 2017, Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors, Science, 356, 10.1126/science.aah4573 See, 2017, Mapping the human DC lineage through the integration of high-dimensional techniques, Science, 356, 10.1126/science.aag3009 Villar, 2020, The more, the merrier: DC3s join the human dendritic cell family, Immunity, 53, 233, 10.1016/j.immuni.2020.07.014 Villar, 2020, Decoding the heterogeneity of human dendritic cell subsets, Trends Immunol., 10.1016/j.it.2020.10.002 Laurenti, 2018, From haematopoietic stem cells to complex differentiation landscapes, Nature, 553, 418, 10.1038/nature25022 Heidkamp, 2016, Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment, Sci. Immunol., 1, 10.1126/sciimmunol.aai7677 Joffre, 2009, Inflammatory signals in dendritic cell activation and the induction of adaptive immunity, Immunol. Rev., 227, 234, 10.1111/j.1600-065X.2008.00718.x Manicassamy, 2011, Dendritic cell control of tolerogenic responses, Immunol. Rev., 241, 206, 10.1111/j.1600-065X.2011.01015.x Dunn, 2002, Cancer immunoediting: from immunosurveillance to tumor escape, Nat. Immunol., 3, 991, 10.1038/ni1102-991 Wculek, 2020, Dendritic cells in cancer immunology and immunotherapy, Nat. Rev. Immunol., 20, 7, 10.1038/s41577-019-0210-z Scarlett, 2012, Ovarian cancer progression is controlled by phenotypic changes in dendritic cells, J. Exp. Med., 209, 495, 10.1084/jem.20111413 Chen, 2013, Oncology meets immunology: the cancer-immunity cycle, Immunity, 39, 1, 10.1016/j.immuni.2013.07.012 Leal, 2021, Innate cell microenvironments in lymph nodes shape the generation of T cell responses during type I inflammation, Sci. Immunol., 6, 10.1126/sciimmunol.abb9435 Zilionis, 2019, Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species, Immunity, 50, 1317, 10.1016/j.immuni.2019.03.009 Maier, 2020, A conserved dendritic-cell regulatory program limits antitumour immunity, Nature, 580, 257, 10.1038/s41586-020-2134-y Qian, 2020, A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling, Cell Res., 30, 745, 10.1038/s41422-020-0355-0 Zhang, 2019, Landscape and dynamics of single immune cells in hepatocellular carcinoma, Cell, 179, 829, 10.1016/j.cell.2019.10.003 Zhang, 2020, Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer, Cell, 181, 442, 10.1016/j.cell.2020.03.048 Gerhard, 2021, Tumor-infiltrating dendritic cell states are conserved across solid human cancers, J. Exp. Med., 218, 10.1084/jem.20200264 Guilliams, 2014, Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny, Nat. Rev. Immunol., 14, 571, 10.1038/nri3712 Cabeza-Cabrerizo, 2019, Tissue clonality of dendritic cell subsets and emergency DCpoiesis revealed by multicolor fate mapping of DC progenitors, Sci. Immunol., 4, 10.1126/sciimmunol.aaw1941 Salmon, 2016, Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition, Immunity, 44, 924, 10.1016/j.immuni.2016.03.012 Crozat, 2010, The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells, J. Exp. Med., 207, 1283, 10.1084/jem.20100223 Crozat, 2011, Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8α+ type, J. Immunol., 187, 4411, 10.4049/jimmunol.1101717 Spranger, 2015, Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity, Nature, 523, 231, 10.1038/nature14404 Montoya, 2002, Type I interferons produced by dendritic cells promote their phenotypic and functional activation, Blood, 99, 3263, 10.1182/blood.V99.9.3263 Diamond, 2011, Type I interferon is selectively required by dendritic cells for immune rejection of tumors, J. Exp. Med., 208, 1989, 10.1084/jem.20101158 Fuertes, 2013, Type I interferon response and innate immune sensing of cancer, Trends Immunol., 34, 67, 10.1016/j.it.2012.10.004 Nejman, 2020, The human tumor microbiome is composed of tumor type-specific intracellular bacteria, Science, 368, 973, 10.1126/science.aay9189 Shi, 2020, Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling, J. Exp. Med., 217, 10.1084/jem.20192282 Laoui, 2016, The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity, Nat. Commun., 7, 13720, 10.1038/ncomms13720 Bachem, 2010, Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells, J. Exp. Med., 207, 1273, 10.1084/jem.20100348 Jongbloed, 2010, Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens, J. Exp. Med., 207, 1247, 10.1084/jem.20092140 Wu, 2017, A critical analysis of the role of SNARE protein SEC22B in antigen cross-presentation, Cell Rep., 19, 2645, 10.1016/j.celrep.2017.06.013 Theisen, 2018, WDFY4 is required for cross-presentation in response to viral and tumor antigens, Science, 362, 694, 10.1126/science.aat5030 Alloatti, 2017, Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity, J. Exp. Med., 214, 2231, 10.1084/jem.20170229 Cebrian, 2011, Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells, Cell, 147, 1355, 10.1016/j.cell.2011.11.021 Briseño, 2016, Distinct transcriptional programs control cross-priming in classical and monocyte-derived dendritic cells, Cell Rep., 15, 2462, 10.1016/j.celrep.2016.05.025 Moussion, 2018, The dendritic cell strikes back, Immunity, 49, 997, 10.1016/j.immuni.2018.12.007 Johnson, 2010, Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration, Int. Immunol., 22, 839, 10.1093/intimm/dxq435 Ohl, 2004, CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions, Immunity, 21, 279, 10.1016/j.immuni.2004.06.014 Roberts, 2016, Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of t cell immunity in melanoma, Cancer Cell, 30, 324, 10.1016/j.ccell.2016.06.003 Yewdall, 2010, CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells, PLoS One, 5, e11144, 10.1371/journal.pone.0011144 Ruhland, 2020, Visualizing synaptic transfer of tumor antigens among dendritic cells, Cancer Cell, 37, 786, 10.1016/j.ccell.2020.05.002 Mikucki, 2015, Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints, Nat. Commun., 6, 7458, 10.1038/ncomms8458 Thompson, 2010, Tumor masses support naive T cell infiltration, activation, and differentiation into effectors, J. Exp. Med., 207, 1791, 10.1084/jem.20092454 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 Enamorado, 2017, Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8(+) T cells, Nat. Commun., 8, 16073, 10.1038/ncomms16073 Duckworth, 2021, Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands, Nat. Immunol., 22, 434, 10.1038/s41590-021-00878-5 Garris, 2018, Successful Anti-PD-1 cancer immunotherapy requires t cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12, Immunity, 49, 1148, 10.1016/j.immuni.2018.09.024 Jansen, 2019, An intratumoral niche maintains and differentiates stem-like CD8 T cells, Nature, 576, 465, 10.1038/s41586-019-1836-5 Satpathy, 2012, Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages, J. Exp. Med., 209, 1135, 10.1084/jem.20120030 Meredith, 2012, Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage, J. Exp. Med., 209, 1153, 10.1084/jem.20112675 Dress, 2019, Plasmacytoid dendritic cells develop from Ly6D(+) lymphoid progenitors distinct from the myeloid lineage, Nat. Immunol., 20, 852, 10.1038/s41590-019-0420-3 Inaba, 1992, Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor, J. Exp. Med., 176, 1693, 10.1084/jem.176.6.1693 Karsunky, 2003, Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo, J. Exp. Med., 198, 305, 10.1084/jem.20030323 Xu, 2007, Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking, J. Immunol., 179, 7577, 10.4049/jimmunol.179.11.7577 Watowich, 2010, Mechanisms regulating dendritic cell specification and development, Immunol. Rev., 238, 76, 10.1111/j.1600-065X.2010.00949.x Fuertes, 2011, Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells, J. Exp. Med., 208, 2005, 10.1084/jem.20101159 Alcántara-Hernández, 2017, High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization, Immunity, 47, 1037, 10.1016/j.immuni.2017.11.001 Cytlak, 2020, Differential IRF8 transcription factor requirement defines two pathways of dendritic cell development in humans, Immunity, 53, 353, 10.1016/j.immuni.2020.07.003 Dutertre, 2019, Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells, Immunity, 51, 573, 10.1016/j.immuni.2019.08.008 Bosteels, 2020, Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection, Immunity, 52, 1039, 10.1016/j.immuni.2020.04.005 Böttcher, 2018, The role of type 1 conventional dendritic cells in cancer immunity, Trends Cancer, 4, 784, 10.1016/j.trecan.2018.09.001 Poulin, 2012, DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues, Blood, 119, 6052, 10.1182/blood-2012-01-406967 Sancho, 2009, Identification of a dendritic cell receptor that couples sensing of necrosis to immunity, Nature, 458, 899, 10.1038/nature07750 Hildner, 2008, Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity, Science, 322, 1097, 10.1126/science.1164206 Meyer, 2018, Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance, Nat. Commun., 9, 1250, 10.1038/s41467-018-03600-6 Theisen, 2019, Batf3-dependent genes control tumor rejection induced by dendritic cells independently of cross-presentation, Cancer Immunol. Res., 7, 29, 10.1158/2326-6066.CIR-18-0138 Qiu, 2020, Cutting edge: Batf3 expression by CD8 t cells critically regulates the development of memory populations, J. Immunol., 205, 901, 10.4049/jimmunol.2000228 Ataide, 2020, BATF3 programs CD8+ t cell memory, Nat. Immunol., 21, 1397, 10.1038/s41590-020-0786-2 Tussiwand, 2015, Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses, Immunity, 42, 916, 10.1016/j.immuni.2015.04.017 Schlitzer, 2013, IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses, Immunity, 38, 970, 10.1016/j.immuni.2013.04.011 Kim, 2020, High amount of transcription factor IRF8 engages AP1-IRF composite elements in enhancers to direct type 1 conventional dendritic cell identity, Immunity, 10.1016/j.immuni.2020.07.018 Heger, 2018, CLEC10A is a specific marker for human CD1c(+) dendritic cells and enhances their toll-like receptor 7/8-Induced cytokine secretion, Front. Immunol., 9, 744, 10.3389/fimmu.2018.00744 Binnewies, 2019, Unleashing Type-2 dendritic cells to drive protective antitumor CD4(+) t cell immunity, Cell, 177, 556, 10.1016/j.cell.2019.02.005 Ferris, 2020, cDC1 prime and are licensed by CD4(+) T cells to induce anti-tumour immunity, Nature, 584, 624, 10.1038/s41586-020-2611-3 Dudziak, 2007, Differential antigen processing by dendritic cell subsets in vivo, Science, 315, 107, 10.1126/science.1136080 Fu, 2020, Plasmacytoid dendritic cells cross-prime naive CD8 T cells by transferring antigen to conventional dendritic cells through exosomes, Proc. Natl. Acad. Sci. U. S. A., 117, 23730, 10.1073/pnas.2002345117 Villadangos, 2008, Antigen-presentation properties of plasmacytoid dendritic cells, Immunity, 29, 352, 10.1016/j.immuni.2008.09.002 Brewitz, 2017, CD8(+) t cells orchestrate pDC-XCR1(+) dendritic cell spatial and functional cooperativity to optimize priming, Immunity, 46, 205, 10.1016/j.immuni.2017.01.003 Persson, 2010, Plasmacytoid dendritic cell-induced migration and activation of NK cells in vivo, Eur. J. Immunol., 40, 2155, 10.1002/eji.200940098 Tel, 2013, Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients, Cancer Res., 73, 1063, 10.1158/0008-5472.CAN-12-2583 Leylek, 2020, Chromatin landscape underpinning human dendritic cell heterogeneity, Cell Rep., 32, 108180, 10.1016/j.celrep.2020.108180 Musumeci, 2019, What makes a pDC: recent advances in understanding plasmacytoid DC development and heterogeneity, Front. Immunol., 10, 1222, 10.3389/fimmu.2019.01222 Deb, 2020, Triggering of the cGAS-STING pathway in human plasmacytoid dendritic cells inhibits TLR9-Mediated IFN production, J. Immunol., 205, 223, 10.4049/jimmunol.1800933 Nierkens, 2011, Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells, Cancer Res., 71, 6428, 10.1158/0008-5472.CAN-11-2154 Terra, 2018, Tumor-derived TGFβ alters the ability of plasmacytoid dendritic cells to respond to innate immune signaling, Cancer Res., 78, 3014, 10.1158/0008-5472.CAN-17-2719 Conrad, 2012, Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells, Cancer Res., 72, 5240, 10.1158/0008-5472.CAN-12-2271 Bruchhage, 2018, IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-α secretion of pDCs, Oncol. Lett., 15, 3985 Sisirak, 2013, Breast cancer-derived transforming growth factor-β and tumor necrosis factor-α compromise interferon-α production by tumor-associated plasmacytoid dendritic cells, Int. J. Cancer, 133, 771, 10.1002/ijc.28072 Aspord, 2014, Melanoma hijacks plasmacytoid dendritic cells to promote its own progression, Oncoimmunology, 3, e27402, 10.4161/onci.27402 Labidi-Galy, 2011, Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer, Cancer Res., 71, 5423, 10.1158/0008-5472.CAN-11-0367 Aspord, 2013, Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL, Cancer Immunol. Res., 1, 402, 10.1158/2326-6066.CIR-13-0114-T Labidi-Galy, 2012, Plasmacytoid dendritic cells infiltrating ovarian cancer are associated with poor prognosis, Oncoimmunology, 1, 380, 10.4161/onci.18801 Ma, 2014, CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy, Cancer Res., 74, 436, 10.1158/0008-5472.CAN-13-1265 Segura, 2013, Human inflammatory dendritic cells induce Th17 cell differentiation, Immunity, 38, 336, 10.1016/j.immuni.2012.10.018 Zhang, 2020, Human regulatory dendritic cells develop from monocytes in response to signals from regulatory and helper t cells, Front. Immunol., 11, 1982, 10.3389/fimmu.2020.01982 Cheng, 2021, A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells, Cell, 184, 792, 10.1016/j.cell.2021.01.010 Dalod, 2014, Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming, EMBO J., 33, 1104, 10.1002/embj.201488027 Miller, 2012, Deciphering the transcriptional network of the dendritic cell lineage, Nat. Immunol., 13, 888, 10.1038/ni.2370 Michea, 2018, Adjustment of dendritic cells to the breast-cancer microenvironment is subset specific, Nat. Immunol., 19, 885, 10.1038/s41590-018-0145-8 Galluzzi, 2020, Consensus guidelines for the definition, detection and interpretation of immunogenic cell death, J. Immunother. Cancer, 8, 10.1136/jitc-2019-000337 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 Diamond, 2018, Exosomes shuttle TREX1-sensitive IFN-stimulatory dsDNA from irradiated cancer cells to DCs, Cancer Immunol. Res., 6, 910, 10.1158/2326-6066.CIR-17-0581 Carozza, 2020, Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity, Nat. Cancer, 1, 184, 10.1038/s43018-020-0028-4 Apetoh, 2007, Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy, Nat. Med., 13, 1050, 10.1038/nm1622 Obeid, 2007, Calreticulin exposure dictates the immunogenicity of cancer cell death, Nat. Med., 13, 54, 10.1038/nm1523 Michaud, 2011, Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice, Science, 334, 1573, 10.1126/science.1208347 Aymeric, 2010, Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity, Cancer Res., 70, 855, 10.1158/0008-5472.CAN-09-3566 Ghiringhelli, 2009, Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors, Nat. Med., 15, 1170, 10.1038/nm.2028 Zhou, 2020, Blockade of the phagocytic receptor MerTK on tumor-associated macrophages enhances P2X7R-dependent STING activation by tumor-derived cGAMP, Immunity, 52, 357, 10.1016/j.immuni.2020.01.014 Ma, 2013, Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells, Immunity, 38, 729, 10.1016/j.immuni.2013.03.003 Vacchelli, 2015, Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1, Science, 350, 972, 10.1126/science.aad0779 Le Naour, 2020, A TLR3 ligand reestablishes chemotherapeutic responses in the context of FPR1 deficiency, Cancer Discov. Sistigu, 2014, Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy, Nat. Med., 20, 1301, 10.1038/nm.3708 Formenti, 2018, Radiotherapy induces responses of lung cancer to CTLA-4 blockade, Nat. Med., 24, 1845, 10.1038/s41591-018-0232-2 Reits, 2006, Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy, J. Exp. Med., 203, 1259, 10.1084/jem.20052494 Zebertavage, 2020, Transcriptional upregulation of NLRC5 by radiation drives STING- and interferon-independent MHC-I expression on cancer cells and t cell cytotoxicity, Sci. Rep., 10, 7376, 10.1038/s41598-020-64408-3 Golden, 2014, Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death, Oncoimmunology, 3, e28518, 10.4161/onci.28518 Widau, 2014, RIG-I-like receptor LGP2 protects tumor cells from ionizing radiation, Proc. Natl. Acad. Sci. U. S. A., 111, E484, 10.1073/pnas.1323253111 Ranoa, 2016, Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs, Oncotarget, 7, 26496, 10.18632/oncotarget.8420 Zheng, 2020, RIG-I-like receptor LGP2 is required for tumor control by radiation therapy, Cancer Res., 10.1158/0008-5472.CAN-20-2324 Vanpouille-Box, 2017, DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity, Nat. Commun., 8, 15618, 10.1038/ncomms15618 Vanpouille-Box, 2018, Toward precision radiotherapy for use with immune checkpoint blockers, Clin. Cancer Res., 24, 259, 10.1158/1078-0432.CCR-16-0037 Burnette, 2011, The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity, Cancer Res., 71, 2488, 10.1158/0008-5472.CAN-10-2820 Lim, 2014, Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells, Cancer Immunol. Immunother., 63, 259, 10.1007/s00262-013-1506-7 Marciscano, 2018, Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy, Clin. Cancer Res., 24, 5058, 10.1158/1078-0432.CCR-17-3427 Sharabi, 2015, Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen, Cancer Immunol. Res., 3, 345, 10.1158/2326-6066.CIR-14-0196 Buchwald, 2020, Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy, J. Immunother. Cancer, 8, 10.1136/jitc-2020-000867 Blair, 2020, Dendritic cell maturation defines immunological responsiveness of tumors to radiation therapy, J. Immunol., 204, 3416, 10.4049/jimmunol.2000194 Liang, 2017, Host STING-dependent MDSC mobilization drives extrinsic radiation resistance, Nat. Commun., 8, 1736, 10.1038/s41467-017-01566-5 Hou, 2018, Non-canonical NF-κB antagonizes STING sensor-mediated DNA sensing in radiotherapy, Immunity, 49, 490, 10.1016/j.immuni.2018.07.008 Lin, 2018, Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression, J. Clin. Invest., 128, 805, 10.1172/JCI96113 Tang, 2018, PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression, J. Clin. Invest., 128, 580, 10.1172/JCI96061 Dammeijer, 2020, The PD-1/PD-L1-checkpoint restrains t cell immunity in tumor-draining lymph nodes, Cancer Cell, 10.1016/j.ccell.2020.09.001 Raeber, 2020, Interleukin-2 signals converge in a lymphoid-dendritic cell pathway that promotes anticancer immunity, Sci. Transl. Med., 12, 10.1126/scitranslmed.aba5464 Oba, 2020, A critical role of CD40 and CD70 signaling in conventional type 1 dendritic cells in expansion and antitumor efficacy of adoptively transferred tumor-specific t cells, J. Immunol., 205, 1867, 10.4049/jimmunol.2000347 Furumoto, 2004, Induction of potent antitumor immunity by in situ targeting of intratumoral DCs, J. Clin. Invest., 113, 774, 10.1172/JCI200419762 Anandasabapathy, 2015, Efficacy and safety of CDX-301, recombinant human Flt3L, at expanding dendritic cells and hematopoietic stem cells in healthy human volunteers, Bone Marrow Transplant., 50, 924, 10.1038/bmt.2015.74 Gilfillan, 2018, Clec9A(+) dendritic cells are not essential for antitumor CD8(+) t cell responses induced by poly I:C immunotherapy, J. Immunol., 200, 2978, 10.4049/jimmunol.1701593 Vonderheide, 2018, The immune revolution: a case for priming, not checkpoint, Cancer Cell, 33, 563, 10.1016/j.ccell.2018.03.008 Ribas, 2018, SD-101 in combination with Pembrolizumab in advanced melanoma: results of a phase ib, multicenter study, Cancer Discov., 8, 1250, 10.1158/2159-8290.CD-18-0280 Walshaw, 2020, Toll-like receptor agonists and radiation therapy combinations: an untapped opportunity to induce anticancer immunity and improve tumor control, Int. J. Radiat. Oncol. Biol. Phys., 108, 27, 10.1016/j.ijrobp.2020.04.020 Spranger, 2018, Impact of oncogenic pathways on evasion of antitumour immune responses, Nat. Rev. Cancer, 18, 139, 10.1038/nrc.2017.117 Ruiz de Galarreta, 2019, Β-catenin activation promotes immune escape and resistance to Anti-PD-1 therapy in hepatocellular carcinoma, Cancer Discov., 9, 1124, 10.1158/2159-8290.CD-19-0074 Peng, 2016, Loss of PTEN promotes resistance to t cell-mediated immunotherapy, Cancer Discov., 6, 202, 10.1158/2159-8290.CD-15-0283 Chen, 2018, Control of T(reg) cell homeostasis and immune equilibrium by Lkb1 in dendritic cells, Nat. Commun., 9, 5298, 10.1038/s41467-018-07545-8 Wang, 2019, LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity, Cell Res., 29, 391, 10.1038/s41422-019-0157-4 Lin, 2010, Dendritic cells integrate signals from the tumor microenvironment to modulate immunity and tumor growth, Immunol. Lett., 127, 77, 10.1016/j.imlet.2009.09.003 Alice, 2018, Amplifying IFN-γ signaling in dendritic cells by CD11c-Specific loss of SOCS1 increases innate immunity to infection while decreasing adaptive immunity, J. Immunol., 200, 177, 10.4049/jimmunol.1700909 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 Zelenay, 2015, Cyclooxygenase-dependent tumor growth through evasion of immunity, Cell, 162, 1257, 10.1016/j.cell.2015.08.015 Monti, 2020, Plasmacytoid dendritic cell impairment in metastatic melanoma by lactic acidosis, Cancers (Basel), 12, 10.3390/cancers12082085