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免疫检查点蛋白(PD-L1 和 CTLA-4)在子宫内膜癌中的作用:预后作用及其与 CD4/CD8 肿瘤浸润淋巴细胞(TILs)比值的相关性。

Immune checkpoint proteins (PD-L1 and CTLA-4) in endometrial carcinoma: prognostic role and correlation with CD4/CD8 tumor infiltrating lymphocytes (TILs) ratio.

机构信息

Department of pathology, Faculty of Medicine, Pathology, Tanta University, Tanta, Egypt.

出版信息

J Immunoassay Immunochem. 2022 Mar 4;43(2):192-212. doi: 10.1080/15321819.2021.1981377. Epub 2021 Oct 26.

DOI:10.1080/15321819.2021.1981377
PMID:34697997
Abstract

Developing the prognostic aspects of endometrial carcinoma through shedding light on immune check point proteins (PD-L1 and CTLA-4) together with Tumor-Infiltrating Lymphocytes (TILs) may help finding new targets for immunotherapy, especially for advanced cases. This study aimed to study the immunohistochemical expression of PD-L1 and CTLA-4 in correlation with tumor infiltrating lymphocytes (TILs) in series of endometrial carcinomas. CTLA-4 showed notably higher frequency of expression in the studied cases than PD-L1. However, both showed significant association across different histopathological subtypes. PD-L1 immunohistochemical expression in studied endometrial carcinomas was significantly associated with low CD4/CD8ratio, high tumor grades, presence of lymph node metastasis and higher tumor stage. CTLA-4 immunohistochemical expression in studied endometrial carcinomas was significantly associated with low CD4/CD8 ratio and high tumor grades but not with tumor stage. Both PD-L1 & CTLA-4 are expressed in subset of endometrial carcinomas with more prevalence of the latter. Both immune checkpoint proteins have significant correlation with different prognostic clinicopathological parameters together with TILs (CD4 & CD8 and their ratio). Increased activated cytotoxic T lymphocytes and PD-L1 expression in endometrial carcinomas may suggest identification of patients' subset of tumors that can be candidates for treatment with immunotherapy.

摘要

通过研究免疫检查点蛋白(PD-L1 和 CTLA-4)与肿瘤浸润淋巴细胞(TILs)在子宫内膜癌中的表达,揭示子宫内膜癌的预后因素,可能有助于寻找免疫治疗的新靶点,特别是针对晚期病例。本研究旨在研究一系列子宫内膜癌中 PD-L1 和 CTLA-4 的免疫组织化学表达与肿瘤浸润淋巴细胞(TILs)的相关性。CTLA-4 在研究病例中的表达频率明显高于 PD-L1。然而,两者在不同的组织病理学亚型之间均有显著相关性。PD-L1 在研究的子宫内膜癌中的免疫组织化学表达与低 CD4/CD8 比值、高肿瘤分级、淋巴结转移存在和较高的肿瘤分期显著相关。CTLA-4 在研究的子宫内膜癌中的免疫组织化学表达与低 CD4/CD8 比值和高肿瘤分级相关,但与肿瘤分期无关。PD-L1 和 CTLA-4 均在子宫内膜癌的亚组中表达,后者更为常见。这两种免疫检查点蛋白都与不同的预后临床病理参数以及 TILs(CD4、CD8 及其比值)有显著相关性。子宫内膜癌中活化的细胞毒性 T 淋巴细胞和 PD-L1 的表达增加可能提示可以识别出具有免疫治疗候选资格的肿瘤患者亚组。

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