Identification and characterization of an alternative cancer-derived PD-L1 splice variant

In this study, we extended this observation by performing a computational analysis of 33 other cancer types as well as human cancer cell lines, and identified additionalPD-L1 isoforms with an exon 4 enrichment expressed in 20 cancers and human cancer cell lines. We demonstrate that cancer cell lines with high expression levels of exon 4-enrichedPD-L1 generate a secreted form of PD-L1. Further biochemical studies of exon 4-enriched PD-L1 demonstrated that this form is secreted and maintains the capacity to bind PD-1 as well as to serve as a negative regulator on T cell function, as measured by inhibition of IL-2 and IFNg secretion. Overall, we have demonstrated that truncated forms of PD-L1 exist in numerous cancer types, and have validated that truncated PD-L1 can be secreted and negatively regulate T cell function.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research