Activation of the acute-phase cascade (APC) has been correlated with outcomes in various
cancers, including
head and neck squamous cell carcinoma (
HNSCC). Primary drivers of the APC are the
cytokines within the
interleukin-6 (IL-6) and
IL-1 families. Plasma levels of
IL-6 family
cytokines/soluble
receptors (IL-6, IL-27, IL-31, OSM,
CNTF, soluble (s-)gp130, s-IL-6Rα) and
IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-)
HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of
IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07),
IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-)
HNSCC patients. The
cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general
therapy and immune
therapy stratification, as well as being future platforms for the development of new
immunotherapy.