Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.
Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.10055
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发表时间：
2016-07-26
期刊：
影响因子：
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通讯作者：
Ochiai A
中科院分区：
文献类型：
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作者：
Hatogai K;Kitano S;Fujii S;Kojima T;Daiko H;Nomura S;Yoshino T;Ohtsu A;Takiguchi Y;Doi T;Ochiai A
抗PD-1抗体免疫治疗食管鳞癌初步显示出良好的疗效。在此，我们使用组织芯片和免疫组织化学方法分析了196例食管鳞癌患者标本中的PD-L1和各种肿瘤浸润性免疫细胞(TIICs)。检测肿瘤细胞(TC)和TIICs中PD-L1的表达，以及淋巴细胞(CD4+、CD8+、FOXP3+、PD-1+)和巨噬细胞(CD68+、CD204+)的浸润情况。PD-L1在TCS和TIIC中的表达分别为18.4%和83.3%。PD-L1在TCS和TIIC中的表达与TIIC中各种类型的TIIC显著相关，尤其是CD8+细胞。PD-L1在TCS和TIICs中的表达与良好的总体生存显著相关，并且结合它们的水平提高了预后的准确性。在调整临床病理因素后，PD-L1在TCS和TIIC中的表达、丰富的PD-1+细胞浸润、高CD8+/FOXP3+比率和CD8+/CD204+比率对预后的影响仍然显著。结论：PD-L1的表达反映了抗肿瘤免疫，PD-1/PD-L1的表达和侵袭效应/免疫抑制细胞的比值有一定的预后价值。抑制PD-1/PD-L1信号和免疫抑制细胞的治疗策略有望用于ESCC患者。
Immunotherapy with anti-PD-1 antibody preliminarily showed promising efficacy for treating esophageal squamous cell carcinoma (ESCC). Herein, we used tissue microarrays and immunohistochemically analyzed PD-L1 and various tumor infiltrating immune cells (TIICs) in specimens from 196 ESCC patients who had undergone curative resection without preoperative therapy. PD-L1 expressions in tumor cells (TCs) and TIICs, as well as infiltration of lymphocytes (CD4+, CD8+, FOXP3+, and PD- 1+) and macrophages (CD68+ and CD204+), were evaluated. PD-L1 was expressed in TCs of 18.4% and in TIICs of 83.3% of these patients. PD-L1 expressions in TCs and TIICs were associated with significant infiltration of various TIIC types, especially CD8+ cells. PD-L1 expressions in both TCs and TIICs were significantly associated with favorable overall survival, and combining their levels enhanced prognostic accuracy. Prognostic impacts of PD-L1 expressions in TCs and TIICs, abundant PD-1+ cell infiltration, a high CD8+/FOXP3+ ratio, and the CD8+/CD204+ ratio remained significant after adjusting for clinicopathological factors. In conclusion, PD-L1 expression reflects anti-tumor immunity, and PD-1/PD-L1 expression and the ratio of infiltrating effector to immune suppressor cells have prognostic value. Therapeutic strategies inhibiting the PD-1/PD-L1 signal and immune suppressor cells are anticipated in ESCC patients.