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 enviro...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-βexpression 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.展开更多
Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular...Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses;nevertheless,the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown.In our study,high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1(NUPR1)as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.展开更多
In the process of checking the raw data1,the authors noticed several inadvertent mistakes occurring in Fig.5a,b,c,d,f that need to be corrected after online publication of the article.During the preparation of Fig.5,t...In the process of checking the raw data1,the authors noticed several inadvertent mistakes occurring in Fig.5a,b,c,d,f that need to be corrected after online publication of the article.During the preparation of Fig.5,the representative image showing TFE3 overexpression antagonized the NUPR1 KD-induced inhibition of OSCC cell proliferation and metastasis,were pasted and placed by mistake.The correct results should be as shown below.The authors apologize for these oversights and declare that these corrections do not affect the description,interpretation,or conclusions detailed in the original manuscript.展开更多
基金supported by the Natural Science Foundation of China (82002851)funding of postdoctoral of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine+2 种基金fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZZ180)funding of academician workstation in HainanShanghai Anticancer Association EYAS PROJECT (SACA-CY21A01)。
文摘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-βexpression 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.
基金This work was supported by the National Natural Science Foundation of China(81802716,32000552)the Natural Science Fund of Hunan Province of China(2020JJ5804)+3 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-037)Shanghai Clinical Research Center for Oral Diseases(19MC1910600)Shanghai Municipal Key Clinical Specialty(shslczdzk01601)Emerging Frontier Technology Joint Research Project(SHDC12018104),the project from Hainan Province Clinical Medical Center.
文摘Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses;nevertheless,the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown.In our study,high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1(NUPR1)as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.
文摘In the process of checking the raw data1,the authors noticed several inadvertent mistakes occurring in Fig.5a,b,c,d,f that need to be corrected after online publication of the article.During the preparation of Fig.5,the representative image showing TFE3 overexpression antagonized the NUPR1 KD-induced inhibition of OSCC cell proliferation and metastasis,were pasted and placed by mistake.The correct results should be as shown below.The authors apologize for these oversights and declare that these corrections do not affect the description,interpretation,or conclusions detailed in the original manuscript.
