Integrated analysis of single‐cell RNA‐seq and bulk RNA‐seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma

Abstract The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour‐associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage‐related clusters. We developed a M2 macrophage‐related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single‐cell sequencing data (GSE139324). We identified three distinct M2 macrophage‐related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage‐related genes significantly impact the development and progression of HNSC. The M2 macrophage‐related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.