Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer
Abstract Cancer/testis antigen (CTA) family is restricted to germline and tumor cells and plays an important role during cancer initiation and progression. Five single‐cell and two bulk RNA‐seq datasets are integrated to screen genes in the CTAs family, revealing that Placenta specific protein 1 (Pl...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202417312 |
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| author | Xiaoyan Meng Zhonglong Liu Lu Zhao Ran Li Luoman Gan Liren Cao Jingjing Sun Lingfang Zhang Yue He |
| author_facet | Xiaoyan Meng Zhonglong Liu Lu Zhao Ran Li Luoman Gan Liren Cao Jingjing Sun Lingfang Zhang Yue He |
| author_sort | Xiaoyan Meng |
| collection | DOAJ |
| description | Abstract Cancer/testis antigen (CTA) family is restricted to germline and tumor cells and plays an important role during cancer initiation and progression. Five single‐cell and two bulk RNA‐seq datasets are integrated to screen genes in the CTAs family, revealing that Placenta specific protein 1 (Plac1) is specifically expressed in head and neck squamous cell carcinoma (HNSCC) cells. Sp1 Transcription (SP1) is identified as a specific regulator of Plac1, which is confirmed by cleavage under targets and tagmentation (CUT&Tag)‐seq. With in vitro experiments, in vivo subcutaneous tumor, and a transgenic autochthonous tumor model, it is revealed that Plac1 expression promotes HNSCC progression by inducing epidermal growth factor receptor endocytosis and recycling to increase PI3K/AKT signaling pathway activity. Then, it is revealed that Plac1+ tumor cells recruit CD4+ T cells via CXCL11/CXCR3 and induce Treg differentiation via PVR/TIGIT, which in turn activates the tumorigenic signaling of Plac1+ tumor cells via LTA/LTBR and forms a reciprocal protumor loop. These findings provide insights into molecular features of CTAs in HNSCC and facilitate the development of personalized treatment strategies. |
| format | Article |
| id | doaj-art-78d6f866ffb84a7e97cf0c687c67bc75 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-78d6f866ffb84a7e97cf0c687c67bc752025-08-20T02:56:12ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202417312Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck CancerXiaoyan Meng0Zhonglong Liu1Lu Zhao2Ran Li3Luoman Gan4Liren Cao5Jingjing Sun6Lingfang Zhang7Yue He8Department of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaDepartment of Oral Pathology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaSuzhou Lingdian Biotechnology Co., Ltd Suzhou 215000 P. R. ChinaDepartment of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 P. R. ChinaAbstract Cancer/testis antigen (CTA) family is restricted to germline and tumor cells and plays an important role during cancer initiation and progression. Five single‐cell and two bulk RNA‐seq datasets are integrated to screen genes in the CTAs family, revealing that Placenta specific protein 1 (Plac1) is specifically expressed in head and neck squamous cell carcinoma (HNSCC) cells. Sp1 Transcription (SP1) is identified as a specific regulator of Plac1, which is confirmed by cleavage under targets and tagmentation (CUT&Tag)‐seq. With in vitro experiments, in vivo subcutaneous tumor, and a transgenic autochthonous tumor model, it is revealed that Plac1 expression promotes HNSCC progression by inducing epidermal growth factor receptor endocytosis and recycling to increase PI3K/AKT signaling pathway activity. Then, it is revealed that Plac1+ tumor cells recruit CD4+ T cells via CXCL11/CXCR3 and induce Treg differentiation via PVR/TIGIT, which in turn activates the tumorigenic signaling of Plac1+ tumor cells via LTA/LTBR and forms a reciprocal protumor loop. These findings provide insights into molecular features of CTAs in HNSCC and facilitate the development of personalized treatment strategies.https://doi.org/10.1002/advs.202417312cancer/testis antigensepithelial growth factor receptorhead and neck squamous cell carcinomaplacenta‐specific protein 1tumor immunitytumor microenvironment |
| spellingShingle | Xiaoyan Meng Zhonglong Liu Lu Zhao Ran Li Luoman Gan Liren Cao Jingjing Sun Lingfang Zhang Yue He Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer Advanced Science cancer/testis antigens epithelial growth factor receptor head and neck squamous cell carcinoma placenta‐specific protein 1 tumor immunity tumor microenvironment |
| title | Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer |
| title_full | Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer |
| title_fullStr | Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer |
| title_full_unstemmed | Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer |
| title_short | Plac1+ Tumor Cell‐Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer |
| title_sort | plac1 tumor cell treg interplay supports tumorigenesis and progression of head and neck cancer |
| topic | cancer/testis antigens epithelial growth factor receptor head and neck squamous cell carcinoma placenta‐specific protein 1 tumor immunity tumor microenvironment |
| url | https://doi.org/10.1002/advs.202417312 |
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