title: Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma.
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 vitrostimulation 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.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Seidel
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Tatsuki R
authors.initials: TR
authors.lastname: Kataoka
authors.affiliation: Department of Dermatology, Niigata Cancer Center Hospital , Chuo-ku, Niigata, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Department of Dermatology, Kagoshima University Faculty of Medicine , Sakuragaoka, Kagoshima, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Dermatology, Kagoshima University Faculty of Medicine , Sakuragaoka, Kagoshima, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.affiliation: Department of Dermatology, University of the Ryukyus , Nishihara, Okinawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okubo
authors.affiliation: Department of Dermatology, University of the Ryukyus , Nishihara, Okinawa, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine , Kita-ku, Sapporo, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Yanagi
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine , Kita-ku, Sapporo, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Hoshina
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine , Kita-ku, Sapporo, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hata
authors.affiliation: Division of Dermatology, Niigata University Graduate School of Medicine and Dental Sciences , Chuo-ku, Niigata, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine , Aoba-ku, Miyagi, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine , Aoba-ku, Miyagi, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Funakoshi
authors.affiliation: Department of Dermatology, Keio University School of Medicine , Shinjyuku-ku, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital , Bunkyo-ku, Tokyo, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Masuzawa
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine , Minami-ku, Sagamihara, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Amoh
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine , Minami-ku, Sagamihara, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Dermatology, University of Tsukuba , Tsukuba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
keywords: Cutaneous angiosarcoma; IFNγ; PD-1; PD-L1; T cells