Starting with the treatment of patients with melanoma, immunomodulation by immune checkpoint inhibitors (ICI) has revolutionized cancer therapy in both palliative and adjuvant settings. Since at best half of the treated patients experience durable clinical benefit, combinatorial ICI protocols have been introduced, resulting in improved efficacy but unfortunately also increased toxicity. 

Recently, in the IMMUNED study, a double-blind, randomized, placebo-controlled trial testing PD-1 blockade by nivolumab alone or in combination with concurrent CTLA-4 inhibition by ipilimumab in patients with stage IV melanoma without evidence of disease, we demonstrated a statistically significant and clinically meaningful benefit for the combination of nivolumab plus ipilimumab, which however had significantly more adverse events. A better understanding of the immunological characteristics of patients who already benefit from PD-1 inhibition alone and those who require combined PD-1 and CTLA-4 blockade would allow appropriate patients to be spared the additional side effects of the combination therapy.

In this funded project, we will conduct an integrative study combining genomic, transcriptomic and spatial proteomic analyses of tumor tissue samples with analyses of immunological and tumor characterizing biomarkers as well as clinical data of patients from the IMMUNED study to develop a clinically applicable prediction model for patient outcomes to the different forms of ICI-based immunotherapy.