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Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy

Nano Research 2024年第9期17卷 8389-8401页

作者： Xianjin Luo Chenglong Li Zhaofei Guo Hairui Wang Penghui He Yuanhao Zhao Yi Lin Chunting He Yingying Hou Yongshun Zhang Guangsheng Du Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China Pharmaceutical Biotechnology Department of PharmacyLMU MunichButenandt Strasse 5-13Munich 81377Germany Department of Biomedical Engineering College of Future TechnologyPeking UniversityBeijing 100871China

Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades,their relatively poor capacity to stimulate immune responses,especially cellular immune responses,has limited their ***,we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and ***,a programmed death-ligand 1(PD-L1)inhibitor,JQ-1,was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells(APCs)upon vaccination,thereby augmenting its anti-tumor *** fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells(BMDCs)in *** subcutaneous vaccination,the nano-vaccines efficiently drained to the tumor-draining lymph nodes(TDLNs),and significantly inhibited PD-L1 expression of both dendritic cells(DCs)and macrophages within the TDLNs and *** a result,the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse *** summary,the fabricated cell membrane-based fusogenic liposomes offer a safe,effective,and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.

关键词： fusogenic liposome tumor cell membrane adjuvant programmed death-ligand 1(PD-L1)inhibitor tumor draining lymph nodes

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Identification and functional analysis of heterogeneous FOXP3^+ Treg cell subpopulations in human pancreatic ductal adenocarcinoma

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Science Bulletin 2018年第15期63卷 972-981页

作者： Gang Yi Shiwei Guo Wenyu Liu Huan Wang Rendong Liu Andy Tsun Gang Jin Bin Li Shanghai Key Laboratory of Bio-energy Crops School of Life Science Shanghai University Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine CAS Center for Excellence in Molecular Cell Science Unit of Molecular Immunology Institute Pasteur of Shanghai Shanghai Institutes for Biological Sciences University of Chinese Academy of Sciences Medical School Chinese Academy of Sciences Department of General Surgery Changhai Hospital Second Military Medical University

CD4^＋ CD25^＋ regulatory T （Treg） cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes （TDLNs） has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4^＋ Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor- and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma （PDAC） and confirmed their functional heterogeneity. Helios^＋ CCR8^＋ Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs. On the contrary, Helios^- CCR8^- Treg cells have impaired suppressive activity, and elevated expression of pro-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios^＋ CCR8^＋ Treg cells and few Helios^- CCR8^- Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.

关键词： Pancreatic ductal adenocarcinoma Regulatory T cells Heterogeneity tumor draining lymph nodes

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