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Metabolic plasticity of T cell fate decision

Chinese Medical Journal 2024年第7期137卷 762-775页

作者： Xiaoli Pan Jiajia Wang lianjun Zhang guideng li Bo Huang National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Key Laboratory of Synthetic Biology Regulatory Element Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei 430030China

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T *** antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory ***,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted *** studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell *** this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory ***,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted *** the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

关键词： T cell immunotherapy T cell differentiation T cell exhaustion Metabolic reprogramming Tumor microenvironment

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肿瘤精准靶向免疫治疗的关键:T细胞受体抗原筛选技术

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中国肿瘤生物治疗杂志 2024年第1期31卷 10-18页

作者：朱润棣李贵登北京协和医学院中国医学科学院系统医学研究院/苏州系统医学研究所免疫与炎症全国重点实验室江苏苏州215123

过继性T细胞疗法在实体瘤治疗中展现了良好的前景,成为目前肿瘤治疗领域的一大研究热点。其中,TCR-T疗法主要通过T细胞受体(TCR)与抗原肽-主要组织相容性复合体(pMHC)的特异性识别,进而激活过继性T细胞的抗肿瘤免疫反应。因此,全面解析... 详细信息

过继性T细胞疗法在实体瘤治疗中展现了良好的前景,成为目前肿瘤治疗领域的一大研究热点。其中,TCR-T疗法主要通过T细胞受体(TCR)与抗原肽-主要组织相容性复合体(pMHC)的特异性识别,进而激活过继性T细胞的抗肿瘤免疫反应。因此,全面解析TCR所靶向的抗原信息有助于提高TCR-T疗法在临床应用中的有效性及安全性。然而,高效、高通量的TCR抗原筛选技术的缺乏限制了TCR-T疗法的发展。近年来,随着高通量测序技术、质谱流式细胞技术和计算生物学的快速发展,研究人员开发了多种TCR抗原筛选技术用于解析TCR及其特异性识别的抗原信息。本文从抗原定向筛选、TCR定向筛选以及双向筛选三方面对TCR抗原筛选技术进行归纳总结,系统介绍其优缺点,展望TCR抗原筛选技术领域的发展前景,为未来抗原筛选技术的开发提供了新思路。

关键词：肿瘤 T细胞受体抗原 TCR抗原筛选技术 TCR-T疗法

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邻近标记技术在膜蛋白相互作用中的研究进展

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中国药科大学学报 2024年第2期55卷 158-166页

作者：裴欣李贵登储卫华中国药科大学生命科学与技术学院南京211198 中国医学科学院苏州系统医学研究所苏州215123

膜蛋白是细胞多种生命活动的主要承担者,膜蛋白之间的相互作用参与调控细胞间的接触与信号传递,并与细胞的分化、成熟息息相关。因此,开发多种深入解析膜蛋白之间相互作用的方法具有重要的理论与现实意义。除了传统的免疫共沉淀方法之外... 详细信息

膜蛋白是细胞多种生命活动的主要承担者,膜蛋白之间的相互作用参与调控细胞间的接触与信号传递,并与细胞的分化、成熟息息相关。因此,开发多种深入解析膜蛋白之间相互作用的方法具有重要的理论与现实意义。除了传统的免疫共沉淀方法之外,新开发的邻近标记技术已经逐渐成为了研究膜蛋白相互作用的重要手段。邻近标记技术主要利用生物工具酶标记与诱饵蛋白相互作用的邻近蛋白,并通过流式细胞术、质谱以及共聚焦显微成像技术等方法检测膜蛋白之间的相互作用。本文着重介绍了近些年来新开发的用于研究膜蛋白相互作用的多种邻近标记技术,并展望了该类技术在膜蛋白相互作用领域未来的发展前景。

关键词：邻近标记技术细胞膜蛋白膜蛋白相互作用工具酶

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T cell cross-reactivity in autoimmune-like hepatitis triggered by COVID-19

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hlife 2023年第1期1卷 57-61页

作者： Yisu liu Yuqian Wang Zhiqiang Peng guideng li Jianwei Wang National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeJiangsuChina Key Laboratory of Synthetic Biology Regulatory Element Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeJiangsuChina NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Over 1000 cases of pediatric hepatitis of unknown etiology have been reported worldwide since the first case was reported in the *** date,the etiology of pediatric hepatitis remains unknown and *** was first suspected to be the cause as it was present in the blood samples of the majority of *** cases have also been tested positive for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].However,it is still unclear how these viruses contribute to pediatric *** the case of a pediatric patient with SARS-CoV-2 infection,the liver biopsy showed acute submassive hepatocyte necrosis,accompanied by a significant increase in T cell infiltration[2].Furthermore,CD8+T cell dominant hepatitis induced by coronavirus disease 2019(COVID-19)vaccination has also been recently reported[3].Although it is known that T cell receptors(TCRs)can discriminate between self-and non-self-antigens,it is now well-accepted that TCRs exhibit cross-reactivity toward similar and even distinct antigen peptides[4].Thus,we hypothesized that following SARS-CoV-2 infection or vaccination,T cells carrying TCRs that recognize self-antigens undergo clonal expansion,which could eventually result in the onset of autoimmune-like hepatitis(Figure 1A).

关键词： autoimmune acute reactivity

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Safety of Curcuma aromatica oil gelatin microspheres administered via hepatic artery

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World Journal of Gastroenterology 2004年第18期10卷 2637-2642页

作者： Shi-guideng Zhi-FengWu Wei-Yingli Zhi-GangYang GangChang Fan-ZheMeng li-liMo SecondAffiliatedHospitalofGuangzhouUniversityofTraditionalChineseMedicine Guangzhou510120GuangdongProvinceChina

AIM: To evaluate the safety of Curcurna aromatica oil gelatin microspheres (CAO-GMS) infused via hepatic artery against primary liver ***: The safety of CAO-GMS was evaluated in view of its acute toxicity in rats, long-term toxicity in Beagle dogs and general pharmacology in rats and mongrel ***: The 50% lethal dose (LDs0) of CAO-GMS infused via the hepatic artery was 17.19 mg/kg, and the serum biochemical indices of dying rats after the administration changed markedly while those of survived rats did *** pathological examination of the tissues from the dead rats indicated improper embolism. Similar edema and small necrotic foci in the hepatic Iobule were found in the hepatic tissue of rats receiving 10 and 5 mg/kg CAO-GMS and GMS 60 d after the last administration, while not in the rats of the blank control group, indicating that microspheres infused via the hepatic artery may induce irreversible liver damage dose-dependently. General pharmacological study showed that the activities (posture and gait), respiration frequency, blood pressure or heart rate of the dogs were not affected by CAO-GMS, nor were salivation, tremor or pupil changes of the rats observed or their balancing ability compromised, suggesting CAO-GMS infused via the hepatic artery did not significantly affect the nervous, respiratory and cardiovascular ***: CAO-GMS embolization administered via the hepatic artery is safe but undesired embolization induced by vascular variation should be given due attention in its clinical application. Individualized embolization dosage and super-selective catheterization technique are recommended to avoid undesired embolism and reduce complications.

关键词：保险装置郁金油微球体凝胶肝动脉肝癌肿瘤

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