Expression of immune checkpoint molecules in endometrial carcinoma

Exp Ther Med. 2015 Nov;10(5):1947-1952. doi: 10.3892/etm.2015.2714. Epub 2015 Aug 28.

Abstract

The main obstacle in the development of an effective tumor vaccine is the inherent ability of tumors to evade immune responses. Tumors often use common immune mechanisms and regulators to evade the immune system. The present study aimed to analyze the expression levels of indoleamine 2,3-dioxygenase (IDO), programmed death-ligand (PD-L) 1, PD-L2, B7-H4, galectin-1 and galectin-3 in tissue samples from patients with endometrial carcinoma, in order to detect the immunosuppressive environment of endometrial carcinomas. The levels of IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemical methods, and the levels of galectin-1 and galectin-3 in tumor lysates were determined using ELISA. PD-L2 was expressed at low levels in the majority of tumor samples. IDO expression was detected in 38, 63 and 43% of primary endometrial carcinoma, recurrent endometrial carcinoma, and metastatic endometrial carcinoma specimens, respectively. Positive expression rates for PD-L1 were 83% in primary endometrial carcinoma, 68% in recurrent endometrial carcinoma, and 100% in metastatic endometrial carcinoma, whereas B7-H4 expression was detected in 100% of both primary endometrial carcinoma and recurrent endometrial carcinoma samples, and in 96% of metastatic endometrial carcinoma specimens. The expression levels of galectin-1 and galectin-3 were not significantly different between the normal and tumor specimens. The results of the present study suggest that the interaction between PD-1/PD-L1 and B7-H4 may be a potential target for immune intervention in the treatment of endometrial carcinoma. Furthermore, the results may provide the basis for immunosuppressant therapy in the treatment of patients with uterine cancer.

Keywords: endometrial carcinoma; immune checkpoint; immunosuppressant.