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Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainly manifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remained 50%, and it has not significantly improved in the past 10 years. Previous studies have shown that the tumor microenvironment (TME) plays a crucial role in the recurrence, metastasis, and drug resistance of patients with HNSCC. In this review, we summarize the role of anti-tumor and pro-tumor immune cells, as well as extracellular components in the TME of HNSCC. We also discuss classical HNSCC immunotherapy and highlight examples of clinical trials using CTLA-4 inhibitors and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1)-related combination therapies. We also outline some molecules in the TME known to regulate immunosuppressive cells. Furthermore, the role and underlying mechanism of radiation therapy on the TME, immune cells, and immune response are discussed.

SUBMITTER: Qin Y

PROVIDER: S-EPMC7878981 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

Qin Yixiao Y Zheng Xiwang X Gao Wei W Wang Binquan B Wu Yongyan Y

Molecular therapy oncolytics 20210121

Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainly manifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remain ...[more]

PMID: 33614915

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Project description:Head and neck squamous carcinoma (HNSCC) is highly infiltrated by immune cells, including tumor-infiltrating lymphocytes and myeloid lineage cells. In the tumor microenvironment, tumor cells orchestrate a highly immunosuppressive microenvironment by secreting immunosuppressive mediators, expressing immune checkpoint ligands, and downregulating human leukocyte antigen expression. In the present study, we aimed to comprehensively profile the immune microenvironment of HNSCC using gene expression data obtained from public database. We calculated enrichment scores of 33 immune cell types based on gene expression data of HNSCC tissues and adjacent non-cancer tissues. Based on these scores, we performed non-supervised clustering and identified three immune signatures-cold, lymphocyte, and myeloid/dendritic cell (DC)-based on the clustering results. We then compared the clinical and biological features of the three signatures. Among HNSCC and non-cancer tissues, human papillomavirus (HPV)-positive HNSCCs exhibited the highest scores in various immune cell types, including CD4+ T cells, CD8+ T cells, B cells, plasma cells, basophils, and their subpopulations. Among the three immune signatures, the proportions of HPV-positive tumors, oropharyngeal cancers, early T tumors, and N factor positive cases were significantly higher in the lymphocyte signature than in other signatures. Among the three signatures, the lymphocyte signature showed the longest overall survival (OS), especially in HPV-positive patients, whereas the myeloid/DC signature demonstrated the shortest OS in these patients. Gene set enrichment analysis revealed the upregulation of several pathways related to inflammatory and proinflammatory responses in the lymphocyte signature. The expression of PRF1, IFNG, GZMB, CXCL9, CXCL10, PDCD1, LAG3, CTLA4, HAVCR2, and TIGIT was the highest in the lymphocyte signature. Meanwhile, the expression of PD-1 ligand genes CD274 and PDCD1LG2 was highest in the myeloid/DC signature. Herein, our findings revealed the transcriptomic landscape of the immune microenvironment that closely reflects the clinical and biological significance of HNSCC, indicating that molecular profiling of the immune microenvironment can be employed to develop novel biomarkers and precision immunotherapies for HNSCC.

Dataset Information

Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

Publications

Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

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