Mice immunized with OVA protein generated OVA-specific skin tissue-resident memory CD8+ T cells (Trm), which rejected OVA-expressing MC38 or B16F10 tumors, leading to systemic expansion of CD8+ T cells specific for non-OVA MC38 or B16F10 antigens (antigen spreading) and suppression of MC38 or B16F10 rechallenge tumors not expressing OVA. Antigen spreading was mediated by Trm-induced maturation of XCR1+ dermal DCs and their subsequent trafficking to tumor-draining lymph nodes. RNAseq data from patients with melanoma showed that the Trm signature correlated with the activated DC signature and with overall survival.
Tissue-resident memory CD8(+) T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8(+) T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8(+) T cell responses through DCs, thereby strengthening anti-tumor immunity.
Author Info: (1) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (2) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (3) Laboratory of Immunoncol
Author Info: (1) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (2) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (3) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (4) Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK. (5) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (6) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (7) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (8) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (9) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. (10) Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK. (11) Laboratory of Immunoncology, Fundacion Ciencia & Vida, Santiago, Chile. alladser@cienciavida.org. Facultad de Medicina y Ciencia, Universidad San Sebastian, Santiago, Chile. alladser@cienciavida.org.
