Bladder Cancer Study Points to Strategy For Enhancing Immunotherapy Response in Tumor Subset

In Cancer Cell, researchers at the Icahn School of Medicine at Mount Sinai and other centers describe a role for the natural killer- and CD8-positive T cell-inhibitory signal mediator NKG2A in bladder cancer response to PD-L1-targeting immune checkpoint blockade treatment. Starting with expression data spanning several cancer types profiled for the Cancer Genome Atlas project, the team saw ties between NKG2A expression and overall survival in individuals with bladder cancer, prompting additional analyses. Using a combination of published data, single-cell RNA sequencing on cells isolated from eight fresh bladder tumor samples, immune cell profiling, and other analyses, the authors teased out relationships between NKG2A-expressing CD8-positive T cells and tumors expressing varying levels and forms of the human leukocyte antigen (HLA). "Notably, NKG2A-positive CD8-positive T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner," they report, adding that "our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E."