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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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Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5048-5059页

作者： Xiaodi Liu Qi Zhang Yixia Liang Shiyu Xiong Yan Cai Jincheng Cao Yanni Xu Xiaolin Xu Ye Wu Qiang Lu Xiaoding Xu Baoming Luo Department of Ultrasound Laboratory of Ultrasound Imaging and DrugWest China HospitalSichuan UniversityChengdu 610041China Department of Ultrasound Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong Provincial Key Laboratory of Malignant tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Ultrasound Central People's Hospital of ZhanjiangZhanjiang 524045China

cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer *** evidence has shown that interferon-gamma(IFN)could enhance CXCL9 secretion from macrophages to recruit t cells,but Siglec15 expressed on tAMs can attenuate t cell ***,targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of t cells in tumor *** herein developed reductionresponsive nanoparticles(NPs)made with poly(disulfide amide)(PDSA)and lipid-poly(ethylene glycol)(lipid-PEG)for systemic delivery of Siglec15 siRNA(siSiglec15)and IFN for enhanced cancer *** intravenous administration,these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages(tAMs).With the highly concentrated glutathione(GSH)in the cytoplasm to destroy the nanostructure,the loaded IFN and si-Siglec15 could be rapidly released,which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for t cell infiltration and silence Siglec15 expression to promote t cell proliferation,leading to significant inhibition of hepatocellular carcinoma(HCC)growth when combining with the immune checkpoint *** strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

关键词： Nanoparticles tumor-associated macrophages Macrophage repolarization t cell infiltration t cell proliferation Cancer immunotherapy Siglec15 Hepatocellular carcinoma

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Immunosuppression in Human Peripheral Blood t Lymphocytes by Fluvastatin

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 649-655页

作者： Li-Hua WU, Yun-Le WAN1, Hai-Yang XIE, Wen-Jin ZHANG, and Shu-Sen ZHENG* Institute of Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China 1Centre of organ transplantation, the Second Affiliated Hospital, School of Medicine, Zhongshan University, Guangzhou 510000, China Institute of Surgery The First Affiliated Hospital School of Medicine Zhejiang UniversityHangzhou 310003 China Centre of organ transplantation The Second Affiliated Hospital School of Medicine Zhongshan UniversityGuangzhou 510000 China

to investigate the immunosuppressive effect of fluvastatin on the PHA-activated t lymphocytes. t lymphocytes were isolated from the blood of healthy volunteers, cell proliferation and the activation mar- kers expression were examined by flow cytometric analysis. Cytokine secretion was assayed by ELISA. LDH-release assay was used to detect activity of killer cells. NFAt activation was evaluated by transAMtM ELISA kit. Results were as following. (1) Whereas no modification in CD25 expression was seen, fluvastatin at 5 μM caused a lower level of CD69 expression, accompanied by an essential suppression on proliferation, IL-2 production and cytotoxicity development in PHA-stimulated t cells. However, the level of secreted IL-10 had no change, and the level of IL-4 even experienced a significant increase. (2) Combined with cyclosporine A (CsA), fluvastatin would further repress CD69 expression, cells proliferation and activity of killer cells, meanwhile significantly induced the secretion of IL-4 and IL-10. (3) Fluvastatin treatment also resulted in a strong inhibition of NFAt activation. In conclusion, partly involving the blockage of activation of NFAt, fluvastatin exhibited an immunosuppressive effect in vitro.

关键词： fluvastatin t cell activation t cell proliferation cytokine nuclear factor of activated tlymphocytes

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