Characterization of B7 members expression in endometrial cancer and clinical significance of PD-L2 in type II subtype

Background: In cancer, up-regulation of co-inhibitory B7 ligands is associated with immune evasion. So far, anti-PD-1 and anti-PD-L1 antibodies has been used in immune-oncology, with promising outcomes but only a small proportion of patients respond successfully. It is still needed identifying other markers, especially for endometrial cancer (EC). EC is a gynecological malignancy classified into two types, endometrioid type I and the most aggressive non-endometrioid type II. Up to now, very few information were provide about B7 members in EC. Furthermore, no molecular prognostic biomarkers are available for type II EC. Objective: Characterization of B7 members profile in EC and evaluation of PD-L2 prognostic impact in human type II EC biopsies. Methods: B7 members were evaluated in six human EC cell lines and one cancer-associated fibroblasts (CAFs), compared to normal endometrial samples. Additionally, using data from cBioportal, we performed a molecular profiling in a cohort of 506 patients. PD-L2 staining was evaluated in a cohort of 23 human type II EC samples, evaluating Overall Survival (OS) and Progression-Free Survival (PFS). Results: EC expresses several B7 members. PD-L2 was significantly over-expressed by one EC Type-I cell line and CAFs, ICOS-L and B7-H4 were expressed especially in mixed type I/II cell lines and type II patients. B7-H3 was expressed in EC cell lines and it was more expressed in type I patients. Additionally to these preliminary data, High PD-L2 expression correlated with shorter OS (p<0.033) but not with PFS (p>0.05). Conclusions: We firstly evidenced that some B7 members were expressed in EC with differences between Type I and Type II, compared with normal tissues. PD-L2 could be a potential predictive biomarker for Type II EC. These preliminary results suggest investigating better the B7 molecular role in EC.