A cytokine-based serum proteomic score is a prognostic biomarker for immunotherapy in head and neck cancer.

Despite advances with anti-programmed death (PD)-1-based immunotherapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), identifying who will benefit from these therapies remains challenging. In a prospective, multicenter study, serum levels of 92 cytokines were measured in pretreatment sera collected on 38 (discovery cohort) and 40 (validation cohort) patients with R/M HNSCC undergoing anti-PD-1-based immunotherapy. A prognostic cytokine score comprised of four cytokines (CXCL1, MCP-4, IL6, CD40) was developed using Cox elastic net modeling within the discovery cohort and showed concordance indices of 0.71 and 0.79 for overall survival (OS) in the discovery and validation cohorts, respectively. High cytokine scores were linked to worse OS (p < 0.01, adjusted HR = 2.07, 95% CI = 1.26-3.41). Further, the cytokine score outperformed established biomarkers including TMB and PD-L1 CPS. Our results suggest that serum cytokine proteomic score may serve as prognostic biomarker for anti-PD-1 therapy in R/M HNSCC.