Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
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...
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| Veröffentlicht in: | Cancer immunology research Jg. 8; H. 2; S. 203 |
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| Sprache: | Englisch |
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01.02.2020
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| ISSN: | 2326-6074, 2326-6074 |
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| 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
and its immunophenotype
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. |
|---|---|
| AbstractList | 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.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. 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 and its immunophenotype 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. |
| Author | Conlon, Christopher P Rosendo-Machado, Samara Chen, Ji-Li Peng, Yanchun Verrill, Clare Fritzsche, Marco Colin-York, Huw Bowes, Emma Cerundolo, Vincenzo Abd Hamid, Megat Maldonado-Perez, David Dong, Tao Yao, Xuan Browne, Molly Cerundolo, Lucia Waugh, Craig Khalid-Alham, Nasullah |
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| Snippet | Enrichment of CD103
tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103... Enrichment of CD103+ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103+... |
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| SubjectTerms | Antigens, CD - immunology Antigens, CD - metabolism CD8-Positive T-Lymphocytes - immunology Humans Immunophenotyping - methods Integrin alpha Chains - immunology Integrin alpha Chains - metabolism Lung Neoplasms - immunology Lung Neoplasms - metabolism Lung Neoplasms - pathology Lymphocytes, Tumor-Infiltrating - immunology Neoplasms - immunology Neoplasms - metabolism Neoplasms - pathology Prognosis Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology T-Lymphocytes, Cytotoxic - immunology Transforming Growth Factor beta1 - immunology Transforming Growth Factor beta1 - metabolism |
| Title | Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses |
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