期刊
INTERNATIONAL IMMUNOLOGY
卷 32, 期 4, 页码 273-281出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxz080
关键词
PD-1(+)CD8(+) T cell; regulatory T cell; tumor microenvironment
类别
资金
- Japan Society for the Promotion of Science [17H06162, 17J09900, 19K22574]
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED) [16cm0106301h0002, 18cm0106340h0001]
- Development of Technology for Patient Stratification Biomarker Discovery grant from the Japan Agency for Medical Research and Development (AMED) [19ae0101074s0401]
- National Cancer Center Research and Development Fund [28-A7, 31-A-7]
- Naito Foundation
- Takeda Science Foundation
- Ono Pharmaceutical Co. Ltd
- Bristol-Myers Squibb
- Grants-in-Aid for Scientific Research [17J09900, 19K22574] Funding Source: KAKEN
Biliary tract cancer (BTC) is an aggressive cancer with a poor prognosis partially due to the limited success in developing novel therapies, including molecularly targeted therapies and immunotherapies. Programmed cell death-1 (PD-1) blockade therapy is less effective against BTCs, necessitating further studies to understand the detailed immunological status of the tumor microenvironment (TME) in BTC. Here, we examined the immunological status of the TME in 37 BTCs with early- to late-stage disease, especially focusing on PD-1(+)CD8(+) T cells. PD-1(+)CD8(+) T cells, which are reportedly associated with the clinical response to PD-1 blockade therapy, were frequently observed in early-stage BTC and decreased with disease progression. Imaging mass cytometry for representative PD-1(+)CD8(+)TIL-high and -low patients demonstrated that tumor-infiltrating PD-1(+)CD8(+) T cells were localized adjacent to tumor cells, whereas PD-1(-)CD8(+) T cells were detected mainly in the stroma of the TME. In a mouse model, PD-1 expression by tumor-infiltrating CD8(+) T cells was higher in smaller tumors and decreased with tumor growth. Consequently, large tumors became resistant to PD-1 blockade, while small tumors containing higher numbers of PD-1(+)CD8(+) T cells were sensitive. We propose the important role of tumor-infiltrating PD-1(+)CD8(+) T cells in anti-tumor immunity and the potential application of PD-1 blockade therapy for early-stage BTC.
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