Immune-based therapies such as the immune checkpoint inhibitors have significantly improved survival rates of metastatic melanoma patients. Anti-tumour activity is further increased by combining different immune checkpoint inhibitors, but toxicity is substantially greater and around one-third of patients still show minimal anti-tumour response. We assessed plasma protein profiles of patients with metastatic melanoma in search of potential biomarkers of response to immune therapy.
Melanoma patients treated with immune checkpoint inhibitor combinations had plasma samples drawn before (baseline) and early during treatment (within 3 weeks of treatment initiation). 12 good responders (classified as complete or partial responders using the immune related RECIST criteria) and 12 poor responders (stable or progressing disease) were retrospectively identified for initial comparison. Plasma samples were evaluated for expression of ~1300 distinct proteins using a novel proteomics assay (SomaLogic).
Proteomic analysis revealed no substantial differences in the baseline plasma of good responders compared to poor responders. In contrast, expression of several proteins including IL-6, the tyrosine-protein kinases Lyn and Fyn were significantly elevated in early during therapy plasma of poor responders compared to good responders. In preliminary functional studies, IL-6 stimulated proliferation of 2 out of 3 melanoma cell lines tested.
The effects of IL-6 on the host-tumour interaction are likely to be protean, but may include a propensity to confer a growth advantage in melanoma cells. These findings indicate IL-6 as a potential marker of poor response to immune checkpoint inhibitors and are being further analysed in an independent validation set.