Hamid et al. compared functionality of TCR-paired CD103+ and CD103- cytotoxic CD8+ T cells (CTLs) specific to cancer testis antigens. CD103+ CTLs showed increased antigen sensitivity, cancer cell killing, and migration rates, dependent on expression of E-cadherin (the CD103 ligand) on target cells. CD103 expression was maintained through autocrine TGFβ1 signaling, and CD103+ CTLs had enhanced metabolic activity and more rapidly apoptosed after prolonged antigen exposure. In patient lung tumors, CD103+ CTLs clustered with E-cadherin-rich tumor areas and expressed inhibitory molecules when the CTLs were CD39high, but not CD39low.
Contributed by Alex Najibi
Enrichment of CD103+ tumor-infiltrating T lymphocytes (TILs) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTLs) and their role in tumor control remains 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 TGFbeta1 to continually self-regulate CD103 expression, without relying on external TGFbeta1-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 co-expression 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 Info: (1) Nuffield Department of Medicine, University of Oxford, CAMS Oxford Institute. (2) MRC Human Immunology Unit, University of Oxford. (3) Department of Engineering Science, Univer
Author Info: (1) Nuffield Department of Medicine, University of Oxford, CAMS Oxford Institute. (2) MRC Human Immunology Unit, University of Oxford. (3) Department of Engineering Science, University of Oxford, Institute for Biomedical Engineering. (4) Nuffield Department of Surgical Sciences, University of Oxford. (5) Ludwig Institute for Cancer Research Ltd, University of Oxford. (6) MRC Human Immunology Unit, University of Oxford. (7) Nuffield Department of Medicine, University of Oxford, CAMS-Oxford joint international Centre for Translational Immunology. (8) MRC Human Immunology Unit, University of Oxford. (9) MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine. (10) University of Oxford. (11) Department of Cellular Pathology, University of Oxford. (12) Nuffield Dept of Surgical Sciences, University of Oxford. (13) MRC Human Immunology Unit,, WIMM, University of Oxford. (14) Nuffield Department of Medicine, University of Oxford. (15) MRC Human Immunology Unit, University of Oxford. (16) RDM investigative medicine, Weatherall Institute of Molecular Medicine. (17) University of Oxford tao.dong@imm.ox.ac.uk.
