Doctoral Program in Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
BMC Cancer. 2020 Feb 17;20(1):127. doi: 10.1186/s12885-020-6545-9.
Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The aim of our study was to investigate the precise prognostic significance of the TME profile in endometrial carcinoma.
We performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients.
High PD-L1 in tumor cells (TCs) was associated with better OS (p = 0.004), whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS (p = 0.02). High PD-L1 in TICs correlated with high densities of CD8 TICs and CD68 TICs, as well as microsatellite instability (p = 0.00000064, 0.00078, and 0.0056), while high PD-L1 in TCs correlated with longer treatment-free interval (TFI) after primary chemotherapy in recurrent cases (p = 0.000043). High density of CD4 TICs correlated with better OS and longer TFI (p = 0.0008 and 0.014). Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4 TICs were significant and independent for favorable OS (p = 0.014 and 0.0025).
The current findings indicate that PD-L1 and CD4 helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.
肿瘤微环境(TME)包括免疫检查点系统,对某些类型的恶性肿瘤的预后有影响。我们的研究目的是探讨 TME 谱在子宫内膜癌中的预后意义。
我们对 221 例子宫内膜癌患者的 TME 蛋白 PD-L1、PD-1、CD4、CD8、CD68 和 VEGF 进行了免疫组化检测。
肿瘤细胞(TCs)中高 PD-L1 与更好的总生存期(OS)相关(p=0.004),而肿瘤浸润免疫细胞(TICs)中高 PD-L1 与更差的 OS 相关(p=0.02)。TICs 中高 PD-L1 与 CD8 TICs 和 CD68 TICs 的高密度相关,也与微卫星不稳定性(MSI)相关(p=0.00000064、0.00078 和 0.0056),而 TCs 中高 PD-L1 与复发性患者原发性化疗后无治疗间隔(TFI)较长相关(p=0.000043)。TICs 中 CD4 密度高与 OS 更好和 TFI 更长相关(p=0.0008 和 0.014)。预后因素的单因素和多因素分析显示,TCs 中高 PD-L1 和 CD4 辅助 T 细胞密度高是 OS 良好的显著独立预后因素(p=0.014 和 0.0025)。
目前的研究结果表明,PD-L1 和 CD4 辅助 T 细胞可能是通过调节化疗敏感性提高生存率的合理靶点,为将免疫疗法纳入子宫内膜癌治疗策略提供了重要意义。