Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer

Background: Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified. Methods: The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of VTCN1 (encoding B7S1) in OvCa were analyzed. The molecular interaction network, Gene Ontology (GO) analysis and Gene set enrichment analysis (GSEA) were used to functionally annotate and predict signaling pathways of VTCN1 in OvCa. Moreover, 32 treatment-naïve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed. Results: B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. VTCN1 expression was significantly correlated with the mRNA expression levels of several other co-inhibitory immune checkpoints. B7S1 protein was found to be highly expressed in CD45⁺CD68⁺ myeloid cells, whereas its putative receptor was expressed in CD8⁺ tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8⁺ TILs. Functional annotations indicated that VTCN1 was involved in regulating T cell-mediated immune responses and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer. Conclusion: In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8⁺ TILs, which could be targeted for cancer immunotherapy.