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
Department of Dermatology, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine , Sakyo-ku, Kyoto, Japan.
Oncoimmunology. 2016 Nov 4;6(1):e1253657. doi: 10.1080/2162402X.2016.1253657. eCollection 2017.
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 ( = 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, = 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. 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.
皮肤血管肉瘤（CAS）是一种预后较差的恶性肉瘤。程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡蛋白1配体1（PD-L1）表达反映抗肿瘤免疫，且与多种癌症患者的预后相关。本研究旨在探讨PD-1/PD-L1表达与CAS预后之间的关系。对106例CAS病例进行免疫组织化学研究，检测PD-L1和PD-1表达，并分析其与患者预后的相关性。通过流式细胞术评估三种CAS细胞系在有无IFNγ刺激情况下的PD-L1表达。共有30.2%的患者样本PD-L1呈阳性，17.9%显示PD-1阳性细胞高浸润。单因素分析显示，PD-1阳性细胞高浸润与肿瘤部位PD-L1表达及Ⅰ期患者的良好生存之间存在显著关系（P = 0.014，对数秩检验）。多变量Cox比例风险回归分析也显示，在调整可能的混杂因素后，肿瘤部位PD-L1表达且PD-1阳性细胞高浸润的患者更有可能获得良好生存（风险比（HR）= 0.38，P = 0.021，95%置信区间（CI）0.16 - 0.86）。CAS样本的免疫荧光染色显示，PD-L1阳性细胞与PD-1阳性细胞和/或IFNγ高表达的肿瘤基质相邻。用IFNγ刺激后，三种已建立的CAS细胞系中有两种细胞系的PD-L1表达增加。我们的结果表明，PD-1/PD-L1表达与CAS进展相关，抗PD-1抗体治疗可能是CAS的一种新的治疗选择。
