Patient-specific HLA-I subtypes predict response to immune checkpoint blockade

Specific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.