Immune landscape in molecular subtypes of human papillomavirus‐negative head and neck cancer

• Published in: Molecular carcinogenesis Vol. 63; no. 1; pp. 120 - 135
• Main Authors: Xie, Mengyu, Chaudhary, Ritu, Slebos, Robbert J. C., Lee, Kyubum, Song, Feifei, Poole, Maria I., Hoening, Dirk S., Noel, Leenil C., Hernandez‐Prera, Juan C., Conejo‐Garcia, Jose R., Chung, Christine H., Tan, Aik Choon
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2024
• Subjects: B‐cell; Cancer therapies; Clinical outcomes; Clinical trials; Gene expression; Head & neck cancer; head and neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Human papillomavirus; Human Papillomavirus Viruses; Humans; Immunotherapy; Isotypes; Lymphocytes B; molecular classification; Papillomavirus Infections - complications; Papillomavirus Infections - genetics; Phenotypes; Precision medicine; Risk factors; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Transcriptomics; translational bioinformatics; tumor immune microenvironment; Tumor Microenvironment; Tumorigenesis; translational bioinformatics; head and neck cancer; B-cell; tumor immune microenvironment; molecular classification
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23640

Head and neck squamous cell carcinomas (HNSCC) remain a poorly understood disease clinically and immunologically. HPV is a known risk factor of HNSCC associated with better outcome, whereas HPV‐negative HNSCC are more heterogeneous in outcome. Gene expression signatures have been developed to classify HNSCC into four molecular subtypes (classical, basal, mesenchymal, and atypical). However, the molecular underpinnings of treatment response and the immune landscape for these molecular subtypes are largely unknown. Herein, we described a comprehensive immune landscape analysis in three independent HNSCC cohorts (>700 patients) using transcriptomics data. We assigned the HPV− HNSCC patients into these four molecular subtypes and characterized the tumor microenvironment using deconvolution method. We determined that atypical and mesenchymal subtypes have greater immune enrichment and exhibit a T‐cell exhaustion phenotype, compared to classical and basal subtypes. Further analyses revealed different B cell maturation and antibody isotypes enrichment patterns, and distinct immune microenvironment crosstalk in the atypical and mesenchymal subtypes. Taken together, our study suggests that treatments that enhances B cell activity may benefit patients with HNSCC of the atypical subtypes. The rationale can be utilized in the design of future precision immunotherapy trials based on the molecular subtypes of HPV− HNSCC.