SA1 - Increased Plasma Interleukin-10 Levels Predict Poor Outcome in Oral Squamous Cell Carcinoma

Abstract: Background: Oral squamous cell carcinoma (OSCC) remains a lethal and biologically heterogeneous disease for which current clinicopathologic staging does not fully capture prognosis. Circulating cytokines reflect tumor-host immune interactions and may provide minimally invasive biomarkers of disease aggressiveness.

Methods: We analyzed 212 patients enrolled in an ongoing multi-institutional prospective OSCC study. Plasma cytokine/chemokine concentrations were collected on the day of surgery and quantified using bead-based multiplex assays. Fresh-frozen tumor specimens underwent bulk RNA-seq. Pain intensity and quality of life (QoL) were measured using the UCSF Oral Cancer Pain Questionnaire, Brief Pain Inventory, and EORTC QLQ-C30 and QLQ-H&N35.

Results: Higher plasma IL-6, IL-8, IL-10, and TNFa levels were associated with late-stage OSCC, and these cytokines were positively correlated with one another (all P < .05), consistent with a coordinated inflammatory profile. Plasma level of VEGFD was associated with lower symptom scores and better QoL (both P < .05), independent of pathologic stage. Using ROC-derived cutoffs, elevated IL-6, IL-8, IL-10, TNFa, TNF, TGFa, and HBEGF were associated with decreased survival (all P < .05). In multivariable Cox models, IL-10 () and TNFa () independently predicted survival. RNA-seq analyses in patients with high IL-10 expression identified ribosome biogenesis, cytoplasmic translation, and focal adhesion as top dysregulated pathways. Higher IL-10 levels were associated with lower inferred monocyte abundance and higher neutrophil abundance.

Conclusions: Plasma cytokine profiles are associated with symptom burden, QoL, and survival in OSCC. IL-10 and TNFa independently predict survival and are linked to translational/ribosomal programs and immune microenvironment shifts, supporting their potential as minimally invasive prognostic biomarkers.