Profiling Serum Oxylipin Metabolites Across Melanoma Subtypes and Immunotherapy Responders

Immunotherapy has significantly improved clinical outcomes for patients with late-stage melanoma, yet a substantial portion of patients fail to respond to these treatments. The variability in responses to immunotherapy, both among individual patients and across different melanoma subtypes, underscores the need to explore the influence of circulating factors such as oxylipins on therapeutic outcomes. This study investigated the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response.

In a retrospective cohort study, serum samples from 43 stage III and stage IV melanoma patients treated at the University of Colorado Hospital from 2010 to 2023 were analyzed via ultra-high-pressure liquid chromatography-mass spectrometry. Melanoma patients were treated with anti-PD-1 monotherapy or combination immune checkpoint inhibitor therapy, and response was assessed using RECIST 1.1 criteria.

We determined that global oxylipin metabolite profiles are largely uniform pre- and post-treatment across melanoma subtypes, including cutaneous, acral, mucosal, and uveal melanoma. Prostaglandin J₂ was more abundant in rare melanoma subtypes, including acral, mucosal, and uveal melanoma, compared to cutaneous melanoma.

Despite limited variation in serum oxylipin molecular species by subtype and response status, we observed significant differences in prostaglandin J₂, which could serve as a potential biomarker for immune checkpoint inhibitor therapy response in melanoma.