Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma

Yuki Honda, Atsushi Otsuka, Sachiko Ono, Yosuke Yamamoto, Judith A. Seidel, Satoshi Morita, Masahiro Hirata, Tatsuki R. Kataoka, Tatsuya Takenouchi, Kazuyasu Fujii, Takuro Kanekura, Yuko Okubo, Kenzo Takahashi, Teruki Yanagi, Daichi Hoshina, Hiroo Hata, Riichiro Abe, Taku Fujimura, Takeru Funakoshi, Koji YoshinoMamiko Masuzawa, Yasuyuki Amoh, Ryota Tanaka, Yasuhiro Fujisawa, Tetsuya Honda, Kenji Kabashima

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n = 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNγ stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p = 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) = 0.38, p = 0.021, 95% confidence interval (CI) 0.16–0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNγ expression. In vitro stimulation with IFNγ increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.

Original languageEnglish
JournalOncoImmunology
DOIs
Publication statusAccepted/In press - 2016 Dec 23
Externally publishedYes

Keywords

  • Cutaneous angiosarcoma
  • IFNγ
  • PD-1
  • PD-L1
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Honda, Y., Otsuka, A., Ono, S., Yamamoto, Y., Seidel, J. A., Morita, S., Hirata, M., Kataoka, T. R., Takenouchi, T., Fujii, K., Kanekura, T., Okubo, Y., Takahashi, K., Yanagi, T., Hoshina, D., Hata, H., Abe, R., Fujimura, T., Funakoshi, T., ... Kabashima, K. (Accepted/In press). Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma. OncoImmunology. https://doi.org/10.1080/2162402X.2016.1253657