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Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy

Science China(Life Sciences) 2021年第4期64卷 534-547页

作者： Chunmei Fan Shanshan Zhang Zhaojian Gong Xiayu Li Bo Xiang Hao Deng Ming Zhou Guiyuan Li Yong Li Wei Xiong Zhaoyang Zeng Xiaoling Li NHC Key Laboratory of Carcinogenesis Humnan Cancer Hospial and the Afiliaed Cancer HospitalXiangva School of MedicineCenral South UniversiyChangsha 410013China Key Laboratory of Carcinogenesis and Cancer Imvasion of the Chinese Minisiry of Education Cancer Research lsite and School of Basic Medical ScienceCentral South UniversitChangsha 410078China Hunan Key Laboralory of Nonresolving Inlammation and Cancer Disease Genome Research Cener the Third Xiangya HospitalCenralSouth UniversityChangsha 410013China Department of Stomatology Xiangva HospitalCentral Souh UniversityChangsha 410078China Department of Oral and Maillofacial Surgery The Second Xiangya HospitalCentral Souh UniversityChangsha 410011China Deparment of Medicine Dan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHousionTexasUSA

Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients.A deeper understanding of how metabolic reprogramming in the tumor microenvironment(TME)regulates immunity remains a major challenge to tumor *** has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune *** cells compete with infiltrating immune cells for nutrients and ***,the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function,and elevated inhibitory signals may favor cancer immune *** major energy sources that supply different immune cell subtypes also undergo *** herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor *** this context,targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.

关键词： tumor microenvironment metabolic reprogramming infiltrating immune cells tumor immune evasion antitumor immunotherapy

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Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion

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Cellular & Molecular Immunology 2023年第8期20卷 867-880页

作者： Hua Yu Tiezhu Shi Linli Yao Dongwei Xu Yufeng Ding Qiang Xia Wei Liu Xiongjun Wang Precise Genome Engineering Centre School of Life SciencesGuangzhou UniversityGuangzhou510006China State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteRen Ji HospitalShanghai Jiaotong University School of MedicineShanghai200240China Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong510630China

To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC *** analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection *** depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell ***,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T *** phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and ***,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in ***,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.

关键词： Nuclear PIGL cMyc PD-1 antibody CCL2/20 tumor immune evasion

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IGSF9 inhibits T cell proliferation and promotes tumor immune escape

IGSF9 inhibits T cell proliferation and promotes tumor immun...

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第十四届全国免疫学学术大会

作者： Yifan Liu Zunling Li BINZHOU MEDICAL UNIVERSITY

Immunotherapy is currently the most likelyway to cure ***,immunocheckpoint inhibitors are the most widely studied and applied in clinical ***,the latest clinical trial results show that PD-1 monoclonal antibodyhas a strong toxic,and only 20% of tumor patients can benefit from it,and80% of tumor patients have no response to this drug,indicating that mosttumors have their own unique immune escape *** extensive screeningin the early stage of this project,it was found that the immunosuppressivereceptor IGSF9 is highly expressed in many tumor tissues,but its role in theoccurrence and development of tumors has not been ***,the mainpurpose of this study was to elucidate the mechanism by which IGSF9 inhibits Tcell proliferation and promotes tumor immune evasion.

关键词： Immunotherapy IGSF9 T cell proliferation tumor immune evasion

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