Research Paper Volume 15, Issue 21 pp 12588—12617

Characterization of the immune cell function landscape in head and neck squamous carcinoma to assist in prognosis prediction and immunotherapy

Wenlun Wang1,2,3, , Zhouyi Zhang1,2, , Wenming Li1,2, , Dongmin Wei1,2, , Jianing Xu1,2, , Ye Qian1,2, , Shengda Cao1,2, , Dapeng Lei1,2, ,

  • 1 Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
  • 2 NHC Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, P.R. China
  • 3 Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China

Received: June 27, 2023       Accepted: October 3, 2023       Published: November 10, 2023
How to Cite

Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: The malignant characteristics of cancer depend not only on intrinsic properties of cancer cells but also on the functions of infiltrating immune cells. In this study, we aimed to investigate the functional landscape of immune cells in head and neck squamous cell carcinoma (HNSCC).

Methods: We employed single-sample gene set enrichment analysis to examine the immunophenotypes of HNSCC based on 29 immune cell functions (ICFs) in TCGA and GSE65858 datasets. We analyzed the clinical features, immune microenvironment, molecular profiles, and biological processes. Additionally, we developed and validated an ICF-based risk score for personalized prognosis prediction. We confirmed the value of the ICF score in our cohort using qRT-PCR and immunohistochemistry. Molecular docking was used to predict potential compounds for immunotherapy.

Results: Three immunophenotypes (Immune-L, Immune-M, and Immune-H) were identified in 769 HNSCC samples. The characteristics of Immune-H were consistent with a “Hot” tumor, Immune-L was similar to a “Cold” tumor, and Immune-M exhibited intermediate features. The ICF risk score was associated with immune checkpoints, infiltrating immune cells, tumor mutation burden, and sensitivities to targeted/chemotherapeutic agents. Gene set variation analysis implicated the involvement of metabolic reprogramming pathways in the high-risk group. The combination of “Tumor Immune Dysfunction and Exclusion” and “Immunophenoscore” algorithms indicated that the low-risk group had a higher likelihood of benefiting from immunotherapy. Finally, we identified Eltrombopag and other compounds that may be beneficial for HNSCC immunotherapy.

Conclusion: Our study provides a novel perspective on the tumor microenvironment of HNSCC, aiding in the understanding of HNSCC heterogeneity and the development of personalized/precision medicine.


ICF: immune cell function; HNSCC: head and neck squamous cell carcinoma; WGCNA: weighted gene co-expression network analysis; GSVA: gene set variation analysis; ICI: immune checkpoint inhibitor; PD-L1: programmed death ligand-1; TME: tumor microenvironment; GSEA: gene set enrichment analysis; PPI: protein-protein interaction; DEG: differentially expressed gene; IRDEG: immune-related differentially expressed gene; PIG: prognosis-related immune gene; TF: transcription factor; TMB: tumor mutation burden; IPS: immunophenoscore; GPI-AP: glycosylphosphatidylinositol-anchored protein.