Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma.
10.1038/s41368-023-00267-8
- Author:
Zheqi LIU
1
,
2
,
3
,
4
,
5
;
Zhen ZHANG
1
,
2
,
3
,
4
,
5
;
Yu ZHANG
1
,
2
,
3
,
4
,
5
;
Wenkai ZHOU
1
,
2
,
3
,
4
,
5
;
Xu ZHANG
1
,
2
,
3
,
4
,
5
;
Canbang PENG
6
;
Tong JI
7
;
Xin ZOU
8
;
Zhiyuan ZHANG
1
,
2
,
3
,
4
,
9
;
Zhenhu REN
1
,
2
,
3
,
4
,
10
Author Information
1. Department of Oral and Maxillofacial - Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
2. College of Stomatology, Shanghai Jiao Tong University
3. National Center for Stomatology
4. National Clinical Research Center for Oral Diseases
5. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
6. School and Hospital of Stomatology, Kunming Medical University, Kunming, China.
7. Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
8. Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China.
9. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. zhzhy0502@163.com.
10. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. 117071@sh9hospital.org.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Carcinoma, Squamous Cell/metabolism*;
Squamous Cell Carcinoma of Head and Neck;
Mouth Neoplasms/metabolism*;
Immunosuppression Therapy;
Transforming Growth Factor beta;
Head and Neck Neoplasms;
Gene Expression Profiling;
Tumor Microenvironment
- From:
International Journal of Oral Science
2024;16(1):9-9
- CountryChina
- Language:English
-
Abstract:
Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
