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

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⁺/CD8⁺ratio, 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.