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...
| Päätekijät: | , , , , , , , , , , , , , , , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
American Association for Cancer Research
2019
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| _version_ | 1826304593475141632 |
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| author | Abd Hamid, M Colin-York, H Khalid-Alham, N Browne, M Cerundolo, L Chen, J-L Yao, X Rosendo-Machado, S Waugh, C Maldonado-Perez, D Bowes, E Verrill, C Cerundolo, V Conlon, CP Fritzsche, M Peng, Y Dong, T |
| author_facet | Abd Hamid, M Colin-York, H Khalid-Alham, N Browne, M Cerundolo, L Chen, J-L Yao, X Rosendo-Machado, S Waugh, C Maldonado-Perez, D Bowes, E Verrill, C Cerundolo, V Conlon, CP Fritzsche, M Peng, Y Dong, T |
| author_sort | Abd Hamid, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:20:11Z |
| format | Journal article |
| id | oxford-uuid:f275c8e1-4b63-4466-a8cf-f3433fb43b37 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:20:11Z |
| publishDate | 2019 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | oxford-uuid:f275c8e1-4b63-4466-a8cf-f3433fb43b372022-03-27T12:04:12ZSelf-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f275c8e1-4b63-4466-a8cf-f3433fb43b37EnglishSymplectic Elements at OxfordAmerican Association for Cancer Research2019Abd Hamid, MColin-York, HKhalid-Alham, NBrowne, MCerundolo, LChen, J-LYao, XRosendo-Machado, SWaugh, CMaldonado-Perez, DBowes, EVerrill, CCerundolo, VConlon, CPFritzsche, MPeng, YDong, TEnrichment 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. |
| spellingShingle | Abd Hamid, M Colin-York, H Khalid-Alham, N Browne, M Cerundolo, L Chen, J-L Yao, X Rosendo-Machado, S Waugh, C Maldonado-Perez, D Bowes, E Verrill, C Cerundolo, V Conlon, CP Fritzsche, M Peng, Y Dong, T Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title | Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title_full | Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title_fullStr | Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title_full_unstemmed | Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title_short | Self-maintaining CD103+ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses |
| title_sort | self maintaining cd103 cancer specific t cells are highly energetic with rapid cytotoxic and effector responses |
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