首页|Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 维普
  • 万方数据
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.

Zheqi Liu、Zhen Zhang、Yu Zhang、Wenkai Zhou、Xu Zhang、Canbang Peng、Tong Ji、Xin Zou、Zhiyuan Zhang、Zhenhu Ren

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Department of Oral and 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 Research Institute of Stomatology,Shanghai,China

Department of Oral and Maxillofacial Surgery,Zhongshan Hospital,Fudan University,Shanghai,China

School and Hospital of Stomatology,Kunming Medical University,Kunming,China

Center for Tumor Diagnosis&Therapy,Jinshan Hospital,Fudan University,Shanghai,China

Department of Pathology,Jinshan Hospital,Fudan University,Shanghai,China

Hainan Western Central Hospital,Academician Zhang Zhiyuan Team Innovation Center,Danzhou,China

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Natural Science Foundation of Chinafunding of postdoctoral of Shanghai Ninth People's HospitalShanghai Jiao Tong University School of Medicinefundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicinefunding of academician workstation in Hainan,Shanghai Anticancer Association EYAS PROJECT

82002851JYZZ180SACA-CY21A01

2024

10.1038/s41368-023-00267-8

国际口腔科学杂志(英文版)
四川大学

国际口腔科学杂志(英文版)

CSTPCD
影响因子：0.684
ISSN：1674-2818
年,卷(期)：2024.16(1)
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