Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Cancer Immunol Res. 2020 Feb;8(2):203-216. doi: 10.1158/2326-6066.CIR-19-0554. Epub 2019 Nov 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Antigens, CD
  • Integrin alpha Chains
  • Receptors, Antigen, T-Cell
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • alpha E integrins