AUTHOR=Cai Dongli , Wang Fang , Wang Changgang , Jin Liping 

TITLE=Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.686803

DOI=10.3389/fmolb.2021.686803

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of <italic>VTCN1</italic> (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 <italic>VTCN1</italic> in OvCa. Moreover, 32 treatment-naïve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed.</p><p><bold>Results:</bold> B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. <italic>VTCN1</italic> 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<sup>+</sup>CD68<sup>+</sup> myeloid cells, whereas its putative receptor was expressed in CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8<sup>+</sup> TILs. Functional annotations indicated that <italic>VTCN1</italic> 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.</p><p><bold>Conclusion:</bold> In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8<sup>+</sup> TILs, which could be targeted for cancer immunotherapy.</p>