Project summary

Blocking immune checkpoints like PD-1 and CTLA-4 is a key cancer treatment. The IMMUNED study showed that combining PD-1 and CTLA-4 blockers improves recurrence-free survival in stage IV melanoma more than PD-1 alone—but with higher side effects. To better match patients to the right treatment, the research team analyzed tumor samples and blood from IMMUNED patients using detailed genetic and immune profiling. While no single clear gene or protein expression-based marker was found to guide therapy choice, it was discovered that tumors with high genomic instability, i.e. high copy-number-variation (CNV) burden, only rarely benefit PD-1 monotherapy, but responded well to a dual checkpoint blockade. This CNV burden, detectable already by a blood test, also relates to immune activity in the tumor and in the blood. If confirmed in larger studies, CNV testing could become a useful, affordable tool to personalize melanoma immunotherapy.