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Regulatory T cells expressing abundant CTLA-4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer |
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| Authors: | Takuma Matoba Masaki Imai Naganari Ohkura Daisuke Kawakita Kei Ijichi Tatsuya Toyama Akimichi Morita Shingo Murakami Shimon Sakaguchi Sayuri Yamazaki |
| Affiliation: | 1. Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Oto-rhino-laryngology and 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. 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;4. Department of Oto-rhino-laryngology and Head-and-neck-surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;5. Department of Oto-rhino-laryngology and Head-and-neck-surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Akaike Oto-rhino-laryngology and Head-and-neck-surgery Clinic, Nisshin, Japan;6. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;7. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;8. Department of Oto-rhino-laryngology and Head-and-neck-surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Oto-rhino-laryngology, Nagoya City East Medical Center, Nagoya, Japan;9. Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka, Japan |
| Abstract: | FOXP3+ regulatory T (Treg) cells suppress anti-tumor immunity. The suppression of Treg cells is regulated by cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), whose expression on the cell surface is tightly regulated. Here we found that Treg cells expressing abundant CTLA-4 on the cell surface (surface-CTLA-4+ Treg) were expanded in human head and neck cancer tissues. RNA sequencing of surface-CTLA-4+ and surface-CTLA-4− Treg cells infiltrating human head and neck cancer tissues revealed that surface-CTLA-4+ Treg cells have a previously undescribed gene expression profile correlating to cell cycle, cell proliferation, and DNA replication. Moreover, surface-CTLA-4+ Treg cells were PD-1+, actively proliferated and associated with CD45RA− FOXP3high Treg cells with strong suppressive function. Thus, surface-CTLA-4+ Treg cells with a proliferative gene expression signature and phenotype are key features of head and neck cancer. Targeting surface-CTLA-4+ Treg cells might be new strategies to evoke effective immune responses to head and neck cancer. |
| Keywords: | regulatory T cells surface expression of CTLA-4 human head and neck cancer RNA sequencing |