Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity
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Published:2024-04-01
Issue:5
Volume:25
Page:834-846
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ISSN:1529-2908
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Container-title:Nature Immunology
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language:en
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Short-container-title:Nat Immunol
Author:
Hamid Megat H. B. A.ORCID, Cespedes Pablo F.ORCID, Jin Chen, Chen Ji-Li, Gileadi UziORCID, Antoun Elie, Liang ZhuORCID, Gao FeiORCID, Teague Renuka, Manoharan Nikita, Maldonado-Perez David, Khalid-Alham Nasullah, Cerundolo Lucia, Ciaoca Raul, Hester Svenja S., Pinto-Fernández Adán, Draganov Simeon D., Vendrell Iolanda, Liu Guihai, Yao Xuan, Kvalvaag Audun, Dominey-Foy Delaney C. C.ORCID, Nanayakkara CharunyaORCID, Kanellakis NikolaosORCID, Chen Yi-LingORCID, Waugh Craig, Clark Sally-AnnORCID, Clark Kevin, Sopp Paul, Rahman Najib M.ORCID, Verrill Clare, Kessler Benedikt M.ORCID, Ogg Graham, Fernandes Ricardo A.ORCID, Fisher RomanORCID, Peng Yanchun, Dustin Michael L.ORCID, Dong TaoORCID
Abstract
AbstractCancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.
Publisher
Springer Science and Business Media LLC
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