Co-expression of immune checkpoint protein VISTA and PD-L1 in bladder cancer and their effects on the immune microenvironment

LIANG Hongxia; SONG Minghui; LU Hongbing; XU Xiaopan

doi:10.13276/j.issn.2097-1656.2025.12.012

Abstract：Objective To investigate the co-expression of V-domain Ig suppressor of T cell activation(VISTA)and programmed cell death ligand 1(PD-L1)in bladder cancer and the composition of tumor microenvironment with simultaneous high expression of VISTA and PD-L1 by using the TCGA bladder cancer database and GEO bladder cancer database.Methods The method of multi-group difference analysis was used in this study to compare the differential genes of VISTAlowPD-L1low,VISTAhighPD-L1low and VISTAlowPD-L1high patients by extracting VISTAhighPD-L1high patients from TCGA database and GEO database respectively.GO and KEGG pathway enrichment analyses were performed to screen the same pathways for differential genes enriched.On this basis,the CIBERSORT method was further used to explore the immunoinfiltration characteristics of VISTAhighPD-L1high patients compared with VISTAlowPD-L1low,VISTAhighPD-L1low,and VISTAlowPD-L1high patients.Results In the TCGA and GEO bladder cancer databases,the expression level of humoral immune response was significantly increased in patients with both VISTA and PD-L1 high expression,which was related to the activity of cytokines,multiple immune pathways and the regulation of immune function in vivo,as well as CD8+T cells and activated dendritic cells.Conclusion In this study,through the analysis of TCGA and GEO bladder cancer databases,it is found that the simultaneous high expression of VISTA and PD-L1 is related to the positive regulation of humoral immune response,which shows typical characteristics different from tumor immunosuppressive microenvironment,and may have new guiding significance for bladder cancer immunotherapy.