Characterization of the Immune Cell Infiltration Landscape in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy

TLDR

The tumor microenvironment in head and neck squamous cell carcinoma consists of tumor cells, immune cells, and stroma, and recent trials link immune cell infiltration to immunotherapy sensitivity and prognosis, yet the detailed infiltration landscape remains undefined. The study proposes two computational algorithms to map the immune cell infiltration landscape in 1,029 HNSC patients. The authors defined three ICI patterns and derived ICI scores through principal‑component analysis using these algorithms. High ICI scores associate with elevated tumor mutation burden, immune‑activating pathways, and superior immunotherapy response, while low scores link to TGF‑β and WNT signaling, T‑cell suppression, and poorer prognosis, confirming ICI scores as a prognostic and predictive biomarker.

Abstract

The tumor microenvironment (TME) chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with the stromal component. A recent clinical trial has shown that the tumor immune cell infiltration (ICI) is correlated with the sensitivity to immunotherapy and the head and neck squamous cell carcinoma (HNSC) prognosis. However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Herein, we proposed two computational algorithms to unravel the ICI landscape of 1,029 HNSC patients. Three ICI patterns were defined, and the ICI scores were determined by using principal-component analysis. A high ICI score was characterized by an increased tumor mutation burden (TMB) and the immune-activating signaling pathways. Activation of transforming growth factor-β (TGF-β) and WNT signaling pathways were observed in low ICI score subtypes, indicating T cell suppression, and may be responsible for poor prognosis. Two immunotherapy cohorts confirmed patients with higher ICI scores demonstrated significant therapeutic advantages and clinical benefits. This study demonstrated that the ICI scores serve as an effective prognostic biomarker and predictive indicator for immunotherapy. Evaluating the ICI patterns of a larger cohort of samples will extend our understanding of TME, and it may provide directions to the current research investigations on immunotherapeutic strategies for HNSC.