Melanoma cells control antimelanoma CTL responses via interaction between TIGIT and CD155 in the effector phase

Takashi Inozume, Tomonori Yaguchi, Junpei Furuta, Kazutoshi Harada, Yutaka Kawakami, Shinji Shimada

研究成果: Article査読

94 被引用数 (Scopus)

抄録

Recently, T-cell immunoreceptor with Ig and ITIM domains (TIGIT) was reported as a candidate for novel immune checkpoints. However, the impact of TIGIT on melanoma-specific cytotoxic T lymphocytes in the effector phase remains unclear. In this study, we demonstrated that melanoma cells control antimelanoma cytotoxic T lymphocyte responses via the TIGIT-CD155 interaction in the effector phase. TIGIT is an inhibitory receptor expressed on T cells, and CD155 is one of the cognate ligands expressed on the tumor cells or antigen presenting cells. First, we confirmed that CD155 was constitutively expressed on melanoma cells. We then demonstrated that CD155 on melanoma cells suppressed cytokine release from melanoma-specific cytotoxic T lymphocytes via interaction with TIGIT. Overexpression of CD155 enhanced and its downregulation attenuated the suppressive effect. This suggested that antimelanoma cytotoxic T lymphocyte responses are controlled not only by an imbalance in CD226 (an activating molecule that binds to CD155) and TIGIT expression on T cells but also by the expression levels of CD155 on melanoma cells. In addition, the co-blockade of TIGIT and PD-1 signals synergistically elicited a response of tumor-infiltrating lymphocytes on autologous melanoma cells. These results suggest that the CD155-TIGIT interaction should be blocked for enhancement of antimelanoma immune responses.

本文言語English
ページ(範囲)255-263
ページ数9
ジャーナルJournal of Investigative Dermatology
136
1
DOI
出版ステータスPublished - 2016 1月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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