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Mature dendritic cells enriched in regulatory molecules may control regulatory T cells and the prognosis of head and neck cancer |
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| Authors: | Kiyoshi Minohara Masaki Imai Takuma Matoba James Badger Wing Hiroaki Shime Mizuyu Odanaka Ryuta Uraki Daisuke Kawakita Tatsuya Toyama Satoru Takahashi Akimichi Morita Shingo Murakami Naganari Ohkura Shimon Sakaguchi Shinichi Iwasaki Sayuri Yamazaki |
| Affiliation: | 1. Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;2. Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;3. Laboratory of Human Immunology (Single Cell Immunology), Immunology Frontier Research Center, Osaka University, Osaka, Japan Human Single Cell Immunology Team, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan;4. Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan;5. Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;6. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;7. Department of Experimental Pathology and Tumor Biology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan;8. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;9. Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka, Japan Department of Frontier Research in Tumor Immunology, Center of Medical Innovation and Translational Research, Graduate School of Medicine, Osaka University, Osaka, Japan;10. Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka, Japan |
| Abstract: | We previously reported that regulatory T (Treg) cells expressing CTLA-4 on the cell surface are abundant in head and neck squamous cell carcinoma (HNSCC). The role of expanded Treg cells in the tumor microenvironment of HNSCC remains unclear. In this study, we reveal that the tumor microenvironment of HNSCC is characterized by the high expression of genes related to Treg cells, dendritic cells (DCs), and interleukin (IL)-17-related molecules. Increased expression of IL17A, IL17F, or IL23A contributes to a favorable prognosis of HNSCC. In the tumor microenvironment of HNSCC, IL23A and IL12B are expressed in mature dendritic cells enriched in regulatory molecules (mregDCs). The mregDCs in HNSCC are a migratory and mature phenotype; their signature genes strongly correlate with Treg signature genes in HNSCC. We also observed that IL17A was highly expressed in Th17 cells and exhausted CD8+ T cells in HNSCC. These data suggest that mregDCs in HNSCC may contribute to the prognosis by balancing Treg cells and effector T cells that produce IL-17. Targeting mregDCs may be a novel strategy for developing new immune therapies against HNSCC. |
| Keywords: | head and neck squamous cell carcinoma (HNSCC) IL-17 mature dendritic cells enriched in regulatory molecules (mregDCs) regulatory T (Treg) cells |