FADD amplification is associated with CD8+ T-cell exclusion and malignant progression in HNSCC
Yang Zheng
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Conceptualization, Investigation, Methodology
Search for more papers by this authorSurui Sheng
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Methodology, Validation
Search for more papers by this authorYanni Ma
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Methodology, Validation
Search for more papers by this authorYinan Chen
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Methodology, Writing - original draft
Search for more papers by this authorRuixin Liu
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Formal analysis, Visualization
Search for more papers by this authorWuchang Zhang
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Supervision
Search for more papers by this authorLi Zhang
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Writing - original draft, Conceptualization, Visualization
Search for more papers by this authorZhonglong Liu
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Validation, Resources
Search for more papers by this authorCorresponding Author
Yue He
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Writing - review & editing, Conceptualization
Search for more papers by this authorCorresponding Author
Hanlin Zeng
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Resources, Funding acquisition
Search for more papers by this authorCorresponding Author
Zhiyuan Zhang
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Conceptualization, Funding acquisition, Writing - review & editing, Supervision
Search for more papers by this authorYang Zheng
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Conceptualization, Investigation, Methodology
Search for more papers by this authorSurui Sheng
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Methodology, Validation
Search for more papers by this authorYanni Ma
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Methodology, Validation
Search for more papers by this authorYinan Chen
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Methodology, Writing - original draft
Search for more papers by this authorRuixin Liu
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Formal analysis, Visualization
Search for more papers by this authorWuchang Zhang
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Supervision
Search for more papers by this authorLi Zhang
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Contribution: Writing - original draft, Conceptualization, Visualization
Search for more papers by this authorZhonglong Liu
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Contribution: Validation, Resources
Search for more papers by this authorCorresponding Author
Yue He
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Writing - review & editing, Conceptualization
Search for more papers by this authorCorresponding Author
Hanlin Zeng
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Resources, Funding acquisition
Search for more papers by this authorCorresponding Author
Zhiyuan Zhang
Department of Oral and Maxillofacial-Head 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, China
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
Correspondence
Zhiyuan Zhang and Yue He, Department of Oral and Maxillofacial-Head 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 Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
Email: [email protected] and [email protected]
Hanlin Zeng, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Precision Medicine, Shanghai 200025, China.
Email: [email protected]
Contribution: Conceptualization, Funding acquisition, Writing - review & editing, Supervision
Search for more papers by this authorYang Zheng, Surui Sheng, and Yanni Ma contributed equally.
Abstract
Objective
This study aimed to clarify the relationship between FADD amplification and overexpression and the tumor immune microenvironment.
Methods
Immunohistochemical staining and bioanalysis were used to analyze the association between FADD expression in tumor cells and cells in tumor microenvironment. RNA-seq analysis was used to detect the differences in gene expression upon FADD overexpression. Flow cytometry and multicolor immunofluorescence staining (mIHC) were used to detect the differences in CD8+ T-cell infiltration in FADD-overexpressed cells or tumor tissues.
Results
Overexpression of FADD significantly promoted tumor growth. Cells with high FADD expression presented high expression of CD276 and FGFBP1 and low expression of proinflammatory factors (such as IFIT1-3 and CXCL8), which reduced the percentage of CD8+ T cells and created a “cold tumor” immune microenvironment, thus promoting tumor progression. In vivo and in vitro experiment confirmed that tumor tissues with excessive FADD expression exhibited CD8+ T-cell exclusion in the microenvironment.
Conclusion
Our preliminary investigation has discovered the association between FADD expression and the immunosuppressive microenvironment in HNSCC. Due to the high frequent amplification of the chromosomal region 11q13.3, where FADD is located, targeting FADD holds promise for improving the immune-inactive state of tumors, subsequently inhibiting HNSCC tumor progression.
CONFLICT OF INTEREST STATEMENT
The authors declare no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| odi14976-sup-0001-TableS1.docxWord 2007 document , 14.4 KB |
Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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