Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma. (2nd January 2017)

• Record Type: Journal Article
• Authors: Honda, Yuki; Otsuka, Atsushi; Ono, Sachiko; Yamamoto, Yosuke; Seidel, Judith A.; Morita, Satoshi; Hirata, Masahiro; Kataoka, Tatsuki R.; Takenouchi, Tatsuya; Fujii, Kazuyasu; Kanekura, Takuro; Okubo, Yuko; Takahashi, Kenzo; Yanagi, Teruki; Hoshina, Daichi; Hata, Hiroo; Abe, Riichiro; Fujimura, Taku; Funakoshi, Takeru; Yoshino, Koji; Masuzawa, Mamiko; Amoh, Yasuyuki; Tanaka, Ryota; Fujisawa, Yasuhiro; Honda, Tetsuya; Kabashima, Kenji
• Is Part Of: Oncoimmunology. Volume 6:Number 1(2017)
• Publication Date: 2017-01-02
• Subjects: Cutaneous angiosarcoma -- IFNγ -- PD-1 -- PD-L1 -- T cells; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1253657
• Languages: English
• ISSNs: 2162-402X

Abstract

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.