Genetic Ancestry and Immunotherapy Response in High-Risk Melanoma

Ahmad Tarhini, MD, PhD, professor and senior member in cutaneous oncology and immunology at Moffitt Cancer Center, discusses inherited genetic variations and genetic ancestry, particularly for patients with high-risk melanoma. With a longstanding focus on improving immunotherapy outcomes and mitigating treatment-related toxicities, Tarhini and his team aim to bridge critical knowledge gaps in precision oncology through this work.

At the 2025 American Association for Cancer Research (AACR) Annual Meeting, Tarhini will be presenting on this research. According to Tarhini, he and his team were particularly interested in studying inherited genetic variations and ancestry among patients with melanoma to better understand both the likelihood of response to immunotherapy and risk of developing immune-mediated adverse events.

This area of research is becoming increasingly relevant, as checkpoint inhibitors and other immunotherapeutic approaches continue to reshape the standard of care for many patients with advanced or high-risk disease.

“We believe this is a bigger question than this study, but we think this is an important first step, especially that the populations included in major clinical trials that lead to regulatory approvals worldwide are not as diverse and representative of a global population as we would like them to be,” explains Tarhini.

This study included patients with melanoma who were treated in the context of a US intergroup phase 3 trial. Patients were required to have regional or distant metastases that continued to be at high risk for melanoma, recurrence, and death.

Once enrolled, patients received either adjuvant immune checkpoint inhibitors or cytokine therapy as part of the trial. To assess genetic variation, the team conducted genome-wide genotyping on biospecimens collected from 744 patients who consented to participate.

“Here, we conducted genome wide genotyping on biospecimens from 744 consenting patients enrolled in the study. Patients were enrolled from sites across the United States and Canada,” adds Tarhini.