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Supplementary Movie Titles and Legends from Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

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posted on 2023-04-04, 01:05 authored by Megat Abd Hamid, Huw Colin-York, Nasullah Khalid-Alham, Molly Browne, Lucia Cerundolo, Ji-Li Chen, Xuan Yao, Samara Rosendo-Machado, Craig Waugh, David Maldonado-Perez, Emma Bowes, Clare Verrill, Vincenzo Cerundolo, Christopher P. Conlon, Marco Fritzsche, Yanchun Peng, Tao Dong

Titles and Legends for Movies 1-4

Funding

CAMS

CIFMS

Medical Research Council

John Fell Fund

Wellcome Trust

EPSRC

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ARTICLE ABSTRACT

Enrichment of CD103+ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103+ CTLs by assessing T-cell receptor (TCR)–matched CD103+ and CD103− cancer-specific CTL immunity in vitro and its immunophenotype ex vivo. Interestingly, we found that differentiated CD103+ cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103+ CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103+ cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.

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    Cancer Immunology Research

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    Keywords

    ImmunologyCytokinesImmune responses to cancerT cell exhaustionLung Cancer

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