Genetic Markers Predict Immunotherapy Response in Melanoma Patients

Recent research has identified four key genes that can forecast how melanoma patients will respond to immunotherapy, a groundbreaking step toward personalized cancer treatment. Melanoma, although representing only about 4% of skin tumors, is highly aggressive and prone to metastasis, contributing to approximately 2,000 deaths annually in Brazil alone. Immunotherapy, especially PD-1 protein blockade, has transformed melanoma management, but it poses challenges due to its high cost and the fact that 40-60% of patients do not respond effectively.

Brazilian researchers at the Molecular Oncology Research Center of Hospital de Amor investigated genetic factors influencing treatment outcomes. Led by Professor Lídia Maria Rebolho Batista Arantes and biotechnological engineer Bruna Pereira Sorroche, the team analyzed tumor samples from 35 advanced melanoma patients treated with anti-PD-1 therapy between 2016 and 2021. They focused on a panel of 579 immune-related genes and discovered four genes—CD24, NFIL3, FN1, and KLRK1—whose elevated expression was strongly associated with resistance to immunotherapy.

Patients exhibiting high levels of these genes were 230 times more likely to not respond to treatment, with a significant decrease in five-year survival rates—only 5.9% of high-expression patients survived, compared to 48.1% with low expression. These genes are involved in immune evasion mechanisms and tumor progression. For example, CD24 acts as an immune checkpoint, helping tumors escape immune detection. FN1 promotes tumor growth structures, while KLRK1, typically activating immune cells, loses its function when dysregulated. NFIL3 influences immune responses, aiding tumor escape.

The findings were validated with data from two international cohorts, confirming the signature's predictive capacity despite variations across groups. The study utilized NanoString technology, an accessible and cost-effective genetic analysis tool, suitable for clinical settings, including resource-limited hospitals. Notably, this genetic signature proved effective even in early-stage melanoma cases, suggesting its potential use from diagnosis to inform treatment strategies.

The research team is working on patenting this approach, aiming to develop a diagnostic panel that assesses gene expression levels prior to therapy. Such a tool could help clinicians identify patients unlikely to benefit from costly immunotherapy, thereby optimizing treatment plans and resource allocation within the public health system, especially the SUS. This innovation has the potential to improve outcomes, reduce unnecessary side effects, and make personalized melanoma treatment more feasible in Brazil.

Despite limitations due to the small sample size and retrospective nature, experts believe these insights pave the way for more precise, cost-effective approaches to melanoma care. Future larger studies are planned to refine the gene expression cutoff for prediction, further integrating this genetic panel into clinical decision-making and advancing personalized oncology in Brazil.

Source: https://medicalxpress.com/news/2025-07-genes-response-immunotherapy-melanoma-patients.html