The potential application of pd-1 blockade therapy for early-stage biliary tract cancer

Kumiko Umemoto, Yosuke Togashi, Yasuhito Arai, Hiromi Nakamura, Shinichiro Takahashi, Tokiyoshi Tanegashima, Mikiya Kato, Tsubasa Nishikawa, Daisuke Sugiyama, Motohiro Kojima, Naoto Gotohda, Takeshi Kuwata, Masafumi Ikeda, Tatsuhiro Shibata, Hiroyoshi Nishikawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)273-281
Number of pages9
JournalInternational Immunology
Volume32
Issue number4
DOIs
Publication statusPublished - Apr 1 2020
Externally publishedYes

Keywords

  • Pd-1+cd8+ t cell
  • Regulatory t cell
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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