Abstract

Endometrial cancer (EC) is among the most prevalent gynecological cancers globally and is recognized as an immunologically regulated tumor in which the tumor microenvironment contributes to immune escape. Natural killer (NK) cells are essential mediators of antitumor immunity; however, their activity may be suppressed through inhibitory receptor pathways, particularly NKG2A/CD94 and KIR/CD158. Thus, the current study aimed to evaluate the immunohistochemical expression of NKG2A/CD94 and KIR/CD158 inhibitory receptors in EC tissues and their association with age and clinicopathological parameters. A case–control study was conducted on 44 endometrial tissue specimens, including 22 histopathologically confirmed EC cases and 22 non-malignant controls collected between October 2024 and March 2025 from three hospitals in Basrah Province, Iraq. Immunohistochemical staining was performed using specific antibodies against CD94 and CD158. The mean age of EC patients was significantly higher than that of controls. Positive CD94 expression was detected in 27.3% of EC tissues and in none of the control tissues, while CD158 expression was significantly higher in EC tissues than in controls. No significant associations were found between expression of inhibitory receptors and clinicopathological parameters. EC is associated with increased expression of NK cell inhibitory receptors, suggesting the presence of an immunoregulatory tumor microenvironment. These findings indicate that inhibitory NK-cell pathways may be involved in immune escape; however, further functional and mechanistic studies are required to confirm their biological and therapeutic significance.

Key words: CD94, CD158, Endometrial cancer, Immune evasion, Microenvironment, Natural killer cells