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

Menares, E; Gálvez-Cancino, F; Cáceres-Morgado, P; Ghorani, E; López, E; Díaz, X; Saavedra-Almarza, J; ... Lladser, A; + view all (2019) Tissue-resident memory CD8⁺ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nature Communications , 10 (1) , Article 4401. 10.1038/s41467-019-12319-x. Green open access

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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.

Type: Article
Title: Tissue-resident memory CD8⁺ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-019-12319-x
Publisher version: https://doi.org/10.1038/s41467-019-12319-x
Language: English
Additional information: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Dendritic cells, Immunization, Immunological memory, Melanoma, Tumour immunology
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10083091
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