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...

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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
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Abstract	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.
AbstractList	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. 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. 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. 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. 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.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.
Author	Dustin, Michael L. Kanellakis, Nikolaos Fisher, Roman Chen, Ji-Li Chen, Yi-Ling Peng, Yanchun Verrill, Clare Pinto-Fernández, Adán Liu, Guihai Gileadi, Uzi Cespedes, Pablo F. Dong, Tao Jin, Chen Fernandes, Ricardo A. Kvalvaag, Audun Antoun, Elie Nanayakkara, Charunya Waugh, Craig Khalid-Alham, Nasullah Vendrell, Iolanda Dominey-Foy, Delaney C. C. Liang, Zhu Teague, Renuka Hester, Svenja S. Sopp, Paul Manoharan, Nikita Clark, Sally-Ann Kessler, Benedikt M. Maldonado-Perez, David Gao, Fei Rahman, Najib M. Ciaoca, Raul Yao, Xuan Cerundolo, Lucia Hamid, Megat H. B. A. Draganov, Simeon D. Clark, Kevin Ogg, Graham
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Snippet	Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer...
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SubjectTerms	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
Title	Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity
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