Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma

Abstract 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, ex...

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Autores principales:	Ikko Mito, Hideyuki Takahashi, Reika Kawabata-Iwakawa, Shota Ida, Hiroe Tada, Kazuaki Chikamatsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a0560d7852a49fca606aa83855221c1
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spelling	oai:doaj.org-article:9a0560d7852a49fca606aa83855221c12021-12-02T19:06:38ZComprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma10.1038/s41598-021-95718-92045-2322https://doaj.org/article/9a0560d7852a49fca606aa83855221c12021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95718-9https://doaj.org/toc/2045-2322Abstract 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.Ikko MitoHideyuki TakahashiReika Kawabata-IwakawaShota IdaHiroe TadaKazuaki ChikamatsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ikko Mito Hideyuki Takahashi Reika Kawabata-Iwakawa Shota Ida Hiroe Tada Kazuaki Chikamatsu Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
description	Abstract 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.
format	article
author	Ikko Mito Hideyuki Takahashi Reika Kawabata-Iwakawa Shota Ida Hiroe Tada Kazuaki Chikamatsu
author_facet	Ikko Mito Hideyuki Takahashi Reika Kawabata-Iwakawa Shota Ida Hiroe Tada Kazuaki Chikamatsu
author_sort	Ikko Mito
title	Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
title_short	Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
title_full	Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
title_fullStr	Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
title_full_unstemmed	Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
title_sort	comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a0560d7852a49fca606aa83855221c1
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Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma

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