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.
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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 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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