Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma

Abstract

Endometrial serous carcinoma (ESC) is an uncommon, aggressive type of endometrial cancer. While immune checkpoint blockade has emerged as a promising treatment option for endometrial carcinomas, research on the expression of immune checkpoints that could serve as prospective immunotherapy targets in ESC is limited. We examined the prevalence and prognostic value of LAG-3, TIGIT, VISTA, and IDO1 in 94 cases of ESC and correlated their expression with CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). We observed a positive correlation between LAG-3, TIGIT and VISTA expressed on immune cells, and between these markers and CD8+ and FOXP3+ TIL density. In Kaplan-Meier survival analysis, tumors with high levels of LAG-3 and TIGIT expression had better progression free survival (PFS) and overall survival (OS) than those with lower levels of expression (LAG-3: PFS, p=0.03, OS, p=0.04; TIGIT: PFS, p=0.01, OS, p=0.009). In multivariate analysis, only high TIGIT expression was of independent prognostic value for better overall survival. VISTA expression in immune or tumor cells, and IDO1 expression in tumor cells, did not show a significant association with survival. Our data indicate that LAG-3, TIGIT, and VISTA immune checkpoints have roles in the microenvironment of ESC, and their expression patterns highlight the complex interactions among the different components of this system. High levels of these markers, together with high CD8+ TIL, suggests the potential immunogenicity of a subset of these tumors. Further studies are needed to elucidate the roles of various immune components in the ESC microenvironment and their association with intrinsic tumor properties.