Cytokines and chemokines in plasma as markers reflecting immunophenotype of head and neck squamous cell carcinoma.

Cancer immunophenotypes-immune desert (ID), immune excluded (IE), and immune inflamed (II)-reflect intratumoral immune activity and correlate with immunotherapy efficacy. Serological methods for non-invasive immunophenotyping would be clinically valuable for selecting therapies. We measured plasma concentrations of cytokines (IL-6, IL-10, IL-16, IL-18, VEGF), chemokines (CXCL9, CXCL13), and soluble membrane molecules (sPD-1, sPD-L1, sCTLA-4, sCD163) in 49 patients with head and neck squamous cell carcinoma (HNSCC) and 22 healthy donors using an automated chemiluminescence enzyme immunoassay system. Plasma levels of IL-6, IL-10, VEGF, CXCL9, CXCL13, and sCD163 were significantly higher in patients with HNSCC than in healthy donors. IL-10 levels trended higher in the order ID > IE > II, whereas CXCL9, CXCL13, and sCD163 levels trended higher in the order II > IE > ID. This progressive trend across phenotypes was further enhanced by calculating the ratios of these markers to IL-10. Significantly higher sPD-1 levels were observed in the II phenotype. These results indicate that plasma concentrations and ratios of CXCL9, CXCL13, sCD163, IL-10, and sPD-1 serve as potential surrogate biomarkers reflecting tumor immunophenotypes in HNSCC.