In:
Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 8, No. 2 ( 2020-02-01), p. 203-216
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 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.
Type of Medium:
Online Resource
ISSN:
2326-6066
,
2326-6074
DOI:
10.1158/2326-6066.CIR-19-0554
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2732517-9
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