Article
Tissue-resident memory CD8(+) T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells
Fecha
2019Autor
Menares, Evelyn
Galvez-Cancino, Felipe
Caceres-Morgado, Pablo
Ghorani, Ehsan
Lopez, Ernesto
Diaz, Ximena
Saavedra-Almarza, Juan
Figueroae, Diego A.
Roa, Eduardo
Quezada, Sergio A.
Lladser, Alvaro
Institución
Resumen
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.