Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells

Evelyn Menares, Felipe Gálvez-Cancino, Pablo Cáceres-Morgado, Ehsan Ghorani, Ernesto López, Ximena Díaz, Juan Saavedra-Almarza, Diego A. Figueroa, Eduardo Roa, Sergio A. Quezada and Alvaro Lladser ()
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Evelyn Menares: Laboratory of Immunoncology, Fundación Ciencia & Vida
Felipe Gálvez-Cancino: Laboratory of Immunoncology, Fundación Ciencia & Vida
Pablo Cáceres-Morgado: Laboratory of Immunoncology, Fundación Ciencia & Vida
Ehsan Ghorani: University College London Cancer Institute
Ernesto López: Laboratory of Immunoncology, Fundación Ciencia & Vida
Ximena Díaz: Laboratory of Immunoncology, Fundación Ciencia & Vida
Juan Saavedra-Almarza: Laboratory of Immunoncology, Fundación Ciencia & Vida
Diego A. Figueroa: Laboratory of Immunoncology, Fundación Ciencia & Vida
Eduardo Roa: Laboratory of Immunoncology, Fundación Ciencia & Vida
Sergio A. Quezada: University College London Cancer Institute
Alvaro Lladser: Laboratory of Immunoncology, Fundación Ciencia & Vida

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12319-x

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