Single-cell transcriptome analysis reveals the clinical implications of myeloid-derived suppressor cells in head and neck squamous cell carcinoma.

Abstract

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor that arises in the epithelium of the head and neck regions. Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell populations, which play a powerful role in inhibiting anti-tumor immune response. Herein, we employed a single-cell RNA sequencing (scRNA-seq) dataset to dissect the heterogeneity of myeloid cells. We found that SPP1 ⁺ tumor-associated macrophages (TAMs) and MDSCs were the most abundant myeloid cells in the microenvironment. By cell cluster deconvolution from bulk RNA-seq datasets of larger patient groups, we observed that highly-infiltrated MDSC was a poor prognostic marker for patients' overall survival (OS) probabilities. To better apply the MDSC OS prediction values, we identified a set of six MDSC-related genes (ALDOA, CD52, FTH1, RTN4, SLC2A3, and TNFAIP6) as the prognostic signature. In both training and test cohorts, MDSC-related prognostic signature showed a promising value for predicting patients' prognosis outcomes. Further parsing the ligand-receptor pairs of intercellular communications by CellChat, we found that MDSCs could frequently interact with cytotoxic CD8 ⁺ T cells, SPP1 ⁺ TAMs, and endothelial cells. These interactions likely contributed to the establishment of an immunosuppressive microenvironment and the promotion of tumor angiogenesis. Our findings suggest that targeting MDSCs may serve as an alternative and promising target for the immunotherapy of HNSC.