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

Abstract

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.