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

Author

Listed:
  • 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
    Universidad San Sebastián)

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.

Suggested Citation

  • 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 & Alvaro Llad, 2019. "Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12319-x
    DOI: 10.1038/s41467-019-12319-x
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    Cited by:

    1. Qingnan Zhao & Jiemiao Hu & Lingyuan Kong & Shan Jiang & Xiangjun Tian & Jing Wang & Rintaro Hashizume & Zhiliang Jia & Natalie Wall Fowlkes & Jun Yan & Xueqing Xia & Sofia F. Yi & Long Hoang Dao & Da, 2023. "FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Nekisa Zakeri & Andrew Hall & Leo Swadling & Laura J. Pallett & Nathalie M. Schmidt & Mariana O. Diniz & Stephanie Kucykowicz & Oliver E. Amin & Amir Gander & Massimo Pinzani & Brian R. Davidson & Alb, 2022. "Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Laura C. D. Pomatto-Watson & Monica Bodogai & Oye Bosompra & Jonathan Kato & Sarah Wong & Melissa Carpenter & Eleonora Duregon & Dolly Chowdhury & Priya Krishna & Sandy Ng & Emeline Ragonnaud & Robert, 2021. "Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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