Researchers hunting for immune checkpoint responders

In a PD-L1 gene are associated with increased PD-L1 expression and contribute to tumor cells' escape from immune surveillance across numerous cancers. The authors said cancer patients expressing the variants may show stronger responses to PD-L1 or PD-1 immunotherapy.

Using whole-genome sequencing of patient samples and RNA sequencing data from the Cancer Genome Atlas (TCGA), the researchers identified several structural variations, including deletions, inversions, duplications and translocations, that disrupt the 3' untranslated region (UTR) of the PD-L1 gene and stabilize it, increasing PD-L1 expression. Disruption of the 3' UTR in T cells prevented tumor regression in mice treated with an immunostimulant, while an anti-PD-L1 antibody shrank tumors in mice expressing the variant. ...