VISTA drives pancreatic tumor progression through modulation of the tumor-associated macrophage polarity.

P-selectin Glycoprotein Ligand-1 (PSGL-1) has been identified as a potential binding partner for VISTA under acidic conditions-common in TME- suggesting that VISTA-PSGL-1 interactions may be significant in regulating immune cell function under these conditions 58 , 59 .

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To extend these findings to human disease, multiplex IF analysis of a limited number of PDAC specimens revealed that, although overall CD8+ T cell infiltration showed an increasing trend with advancing tumor grade, the fraction of CXCR3+ cells within the CD8+ T cell compartment was significantly reduced in grade 2 and grade 3 tumors compared with grade 1 tumors (Supplementary Fig. 19a, b ), demonstrating an inverse relationship between tumor grade and CXCR3 expression.

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