PT  - JOURNAL ARTICLE
AU  - Abd Hamid, Megat
AU  - Colin-York, Huw
AU  - Khalid-Alham, Nasullah
AU  - Browne, Molly
AU  - Cerundolo, Lucia
AU  - Chen, Ji-Li
AU  - Yao, Xuan
AU  - Rosendo-Machado, Samara
AU  - Waugh, Craig
AU  - Maldonado-Perez, David
AU  - Bowes, Emma
AU  - Verrill, Clare
AU  - Cerundolo, Vincenzo
AU  - Conlon, Christopher P.
AU  - Fritzsche, Marco
AU  - Peng, Yanchun
AU  - Dong, Tao
TI  - Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
AID  - 10.1158/2326-6066.CIR-19-0554
DP  - 2020 Feb 01
TA  - Cancer Immunology Research
PG  - 203--216
VI  - 8
IP  - 2
4099  - http://cancerimmunolres.aacrjournals.org/content/8/2/203.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/2/203.full
SO  - Cancer Immunol Res2020 Feb 01; 8
AB  - 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.