Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity

Cancer 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 im...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature immunology Jg. 25; H. 5; S. 834 - 846
Hauptverfasser: Hamid, Megat H. B. A., Cespedes, Pablo F., Jin, Chen, Chen, Ji-Li, Gileadi, Uzi, Antoun, Elie, Liang, Zhu, Gao, Fei, 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., Nanayakkara, Charunya, Kanellakis, Nikolaos, Chen, Yi-Ling, Waugh, Craig, Clark, Sally-Ann, Clark, Kevin, Sopp, Paul, Rahman, Najib M., Verrill, Clare, Kessler, Benedikt M., Ogg, Graham, Fernandes, Ricardo A., Fisher, Roman, Peng, Yanchun, Dustin, Michael L., Dong, Tao
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.05.2024
Nature Publishing Group
Schlagworte:
631/250/1619/554
631/250/2152/1566/1618
631/250/580
Animals
Antigens
Antigens, CD - immunology
Antigens, CD - metabolism
Antitumor activity
Apyrase
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer therapies
CD103 antigen
Cell Line, Tumor
Cell therapy
Cytotoxicity
Cytotoxicity, Immunologic
Humans
Immunology
Immunotherapy
Infectious Diseases
Integrin alpha Chains - metabolism
Lymphocytes
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - metabolism
Mice
Neoplasms - immunology
Neoplasms - therapy
Phenotypes
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Signal Transduction - immunology
T-Lymphocytes, Cytotoxic - immunology
ISSN:1529-2908, 1529-2916, 1529-2916
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Cancer 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. CD103 + T cells are associated with control over tumors but how this is mediated is unclear. Here the authors show that CD61 colocalizes and functionally combines with CD103 in the T cell synaptic response to promote antitumor T cell responses.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-024-01802-3