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 anti-cancer immune activity and is associated with clinical efficacy in immunotherapy such as immune checkpoint inhibitors. The immunophenotypes are pathologically classified in general, if serological classification without resection will be available, it is useful to determine first line therapy. We measured the 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 peripheral plasma samples from 49 of patients with head and neck squamous cell carcinoma (HNSCC) and 22 of healthy donors with chemiluminescence enzyme immunosorbent assay system and evaluated their relationship with each patient's immunophenotype. The concentrations of IL-6, 10, VEGF, CXCL9, CXCL13 and sCD163 in HNSCC patients were significantly higher than healthy donors. IL-10 was trended to be higher in order of ID, IE and II and in contrast, those of CXCL9, CXCL13, sCD163 trended to be higher in order of II, IE and ID. This tendency was further strengthened when the ratios of CXCL9, CXCL13, and sCD163 to IL-10 were calculated. The same tendency was found with a statistically significant difference for sPD-1. Plasma concentrations of IL-6, 10, VEGF, CXCL9, CXCL13 and sCD163 in HNSCC patients likely reflect expression level in the cancer tissue. In addition, the ratio of plasma concentration such as CXCR9/IL-10, CXCR13/IL-10 sCD163/IL-10 and sPD-1 plasma concentration are possible biomarkers for tumoral immunophenotype.