Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma

• Published in: Technology in cancer research & treatment Vol. 20; p. 15330338211045823
• Main Authors: Sun, Jing, Fang, Guiqing, Zuo, Zhibin, Yu, Xijiao, Xue, Lande, Li, Chong, Li, Shu
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2021; Sage Publications Ltd; SAGE Publishing
• Subjects: Algorithms; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; CTLA-4 protein; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Genotypes; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immune Checkpoint Proteins - genetics; Immune Checkpoint Proteins - metabolism; Immune response; Immunostimulation; Immunotherapy; Lymphocytes, Tumor-Infiltrating - immunology; Major histocompatibility complex; Male; Malignancy; Medical prognosis; Middle Aged; Mutation; Original; PD-1 protein; PD-L1 protein; Point mutation; Prognosis; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Survival Rate; Tumors; bioinformatic; immune; prognosis; immune checkpoint; head and neck squamous cell carcinoma; immunocyte
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/15330338211045823

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC