Overview

• Analysis of more than 1,200 patients in the CheckMate-067 Phase 3 trial showed that HG-T carriers were approximately 3.5 times less likely to respond to immune checkpoint inhibitors than non-carriers.
• Validation with nearly 400 additional metastatic melanoma cases from the International Germline Immuno-Oncology Melanoma Consortium confirmed the association between HG-T and reduced therapy benefit.
• Patients harboring HG-T exhibited a higher prevalence of underdeveloped T cells, which researchers traced to enhanced resistance to reactive oxygen species that impedes T cell differentiation.
• The study, led by investigators at NYU Langone Health and its Perlmutter Cancer Center, was published in Nature Medicine on June 5, 2025.
• Prospective clinical trials are planned to evaluate whether stratifying patients by mitochondrial haplogroup can improve immunotherapy outcomes and may extend to other cancer types.