典型文献
Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics
文献摘要：
Colorectal cancer(CRC),a malignant tumor worldwide consists of microsatellite instability(MSI)and stable(MSS)phenotypes.Although SHP2 is a hopeful target for cancer therapy,its relation-ship with innate immunosuppression remains elusive.To address that,single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment(TME)from murine MC38 xenografts.Intratumoral cells were found to be functionally heterogeneous and responded signif-icantly to SHP099,a SHP2 allosteric inhibitor.The malignant evolution of tumor cells was remarkably arrested by SHP099.Mechanistically,STING-TBKl-IRF3-mediated type Ⅰ interferon signaling was highly activated by SHP099 in infiltrated myeloid cells.Notably,CRC patients with MSS phenotype ex-hibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+macrophages than MSI-high phenotypes,suggesting the potential role of macrophagic SHP2 in TME.Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2,suggesting that SHP2 is a promising target for colon cancer immunotherapy.
文献关键词：
中图分类号：
作者姓名：
Jian Gao;Zhigui Wu;Mingxia Zhao;Rui Zhang;Manru Li;Dongdong Sun;Haibo Cheng;Xianjia Qi;Yuxian Shen;Qiang Xu;Hongqi Chen;Dijun Chen;Yang Sun
作者机构：
State Key Laboratory of Pharmaceutical Biotechnology,Chemistry and Biomedicine Innovation Center(ChemBIC),School of Life Sciences,Nanjing University,Nanjing 210023,China;Biopharmaceutical Research Institute,School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China;Department of Colorectal Surgery,Cancer Hospital of China Medical University,Liaoning Cancer Hospital & Institute,Shenyang 110042,China;The First Clinical College of Nanjing University of Chinese Medicine,Nanjing 210023,China;Shanghai XuRan Biotechnology Co.,Ltd.,Shanghai 201109,China;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of General Surgery,Shanghai Jiao Tong University Affiiliated Sixth People's Hospital,Shanghai 200233,China
文献出处：
引用格式：
[1]Jian Gao;Zhigui Wu;Mingxia Zhao;Rui Zhang;Manru Li;Dongdong Sun;Haibo Cheng;Xianjia Qi;Yuxian Shen;Qiang Xu;Hongqi Chen;Dijun Chen;Yang Sun-.Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics)[J].药学学报（英文版）,2022(01):149-166
A类：
SHP099,TBKl,CD68+macrophages,macrophagic
B类：
Allosteric,inhibition,reveals,SHP2,mediated,immunosuppression,colon,cancer,by,single,transcriptomics,Colorectal,CRC,malignant,worldwide,consists,microsatellite,instability,MSI,stable,MSS,phenotypes,Although,hopeful,target,its,relation,ship,innate,remains,elusive,To,address,that,sequencing,was,performed,explore,role,microenvironment,TME,from,murine,MC38,xenografts,Intratumoral,cells,were,found,be,functionally,heterogeneous,responded,signif,icantly,allosteric,inhibitor,evolution,remarkably,arrested,Mechanistically,STING,IRF3,interferon,signaling,highly,activated,infiltrated,myeloid,Notably,patients,hibited,greater,infiltration,more,phosphorylation,than,suggesting,potential,Collectively,our,data,mechanism,promising,immunotherapy
AB值：
0.554132
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