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TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis 被引量:4
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作者 Aizhang Xu Lifeng Zhang +8 位作者 Jingying Yuan Fatma Babikr Andrew Freywald Rajni Chibbar Michael Moser Wenjun Zhang Bing Zhang Zhaoying Fu Jim Xiang 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2019年第10期820-832,共13页
Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstra... Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C,and the 65°C-treated cells are more effective at inducing antigen-specific CD8^(+)cytotoxic T lymphocyte(CTL)responses after injection in mice than the 45°C-treated ones.Dendritic cells(DCs)that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models.RFA(65°C)therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses.This leads to complete regression of small(~100 mm^(3))tumors but fails to suppress the growth of larger(~350 mm^(3))tumors.The administration of the Toll-like receptor-9(TLR9)agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide(CpG)to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses.Importantly,the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b−CD11c^(+)CD103^(+)DC2 and CD11b+F4/80+MHCII+M1 macrophages and increases CD4^(+)and CD8^(+)T-cell tumor infiltration,leading to enhanced CD4^(+)T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors.Overall,our data indicate that CpG administration,which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis,is a promising strategy for improving RFA treatment,which may assist in optimizing this important cancer therapy. 展开更多
关键词 tlr9 agonist RFA CTL response antitumor immunity metastasis
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TLR9激动剂对约氏疟原虫体液免疫记忆的影响
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作者 季迁 刘英杰 《微生物学杂志》 CAS CSCD 2017年第2期89-92,共4页
为探讨TLR9激动剂对疟疾体液免疫记忆的影响,用非致死型约氏疟原虫感染BALB/c小鼠,感染前2 d注射TLR9激动剂CpGl826,90 d后进行二次感染。薄血膜染色法观察红细胞感染率,流式细胞术检测脾细胞悬液中记忆性和活化性B细胞百分比,双夹心EL... 为探讨TLR9激动剂对疟疾体液免疫记忆的影响,用非致死型约氏疟原虫感染BALB/c小鼠,感染前2 d注射TLR9激动剂CpGl826,90 d后进行二次感染。薄血膜染色法观察红细胞感染率,流式细胞术检测脾细胞悬液中记忆性和活化性B细胞百分比,双夹心ELISA法检测特异性抗体水平。结果显示,二次感染前,TLR9激动剂处理鼠记忆性和活化性B细胞以及抗体水平略高于对照组;二次感染后,其再感染发生率和虫血症水平均略低于对照组;活化性B细胞和抗体以及记忆性B细胞也分别于二次感染后1 d和3 d出现了有意义的升高,且升高幅度均略高于对照组。表明TLR9激动剂对约氏疟原虫感染后体液免疫记忆的建立和维持有一定促进作用。 展开更多
关键词 tlr9激动剂 约氏疟原虫 记忆性B细胞 体液免疫
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TLR9激动剂对约氏疟原虫记忆性T细胞的影响
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作者 刘文婷 张宁 《微生物学杂志》 CAS CSCD 2017年第5期77-81,共5页
为探讨TLR9激动剂对疟疾记忆性T细胞的影响,用非致死型约氏疟原虫感染BALB/c小鼠,感染前2 d注射TLR9激动剂Cp Gl826,90 d后进行二次再感染。薄血膜染色法观察虫血症,流式细胞术检测脾细胞悬液中记忆性和活化性T细胞百分率,双夹心ELISA... 为探讨TLR9激动剂对疟疾记忆性T细胞的影响,用非致死型约氏疟原虫感染BALB/c小鼠,感染前2 d注射TLR9激动剂Cp Gl826,90 d后进行二次再感染。薄血膜染色法观察虫血症,流式细胞术检测脾细胞悬液中记忆性和活化性T细胞百分率,双夹心ELISA法检测脾细胞培养上清中细胞因子水平。结果发现,再感染前,TLR9激动剂注射组记忆性T细胞百分率(12.98%)高于对照组(10.16%);再感染后,其再感染发生率(50%)和峰值血症水平(0.64%)均低于对照组(70%和0.82%);而活化性T细胞和IFN-γ水平于再感染后1 d即出现了显著升高,分别达到6.62%和372.74 pg/m L,其升高幅度高于对照组(5.04%和216.17 pg/m L)。这表明,TLR9激动剂对约氏疟原虫记忆性T细胞的产生和维持有一定促进作用。 展开更多
关键词 约氏疟原虫 tlr9激动剂 记忆性T细胞 再感染
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Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine
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作者 Tingting Chen Kan Liu +10 位作者 Jiangyao Xu Tianying Zhan Maixian Liu Li Li Zhiwen Yang Shuping Yuan Wenyi Zou Guimiao Lin Dennis ACarson Christina CNWu Xiaomei Wang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2020年第1期132-141,共10页
Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-bindi... Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-binding transcription factor 4(OCT4),a marker of embryonic stem cells and germ cells,often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.Methods:To identify the optimal carrier and adjuvant combination,we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein,keyhole limpet hemocyanin(KLH),combined with Toll-like receptor 9 agonist(TLR9).Results:Immunization with OCT4-3+TLR9 produced the strongest immune response in mice.In prevention assays,significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3+TLR9(P<0.01).Importantly,the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9.Meanwhile,multiple cytokines[such as interferon(IFN)-γ(P<0.05),interleukin(IL)-12(P<0.05),IL-2(P<0.01),and IL-6(P<0.05)]promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3+TLR9.Moreover,we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.Conclusions:Collectively,these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response,leading to the suppression of primary tumor growth in testis embryonic carcinoma. 展开更多
关键词 Cancer prevention cancer immunology OCT4 tlr9 agonist
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Toll样受体9及其靶向药物研究进展 被引量:1
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作者 叶玲 潘庆军 +1 位作者 唐德燊 刘华锋 《临床医学工程》 2012年第9期1620-1622,共3页
Toll样受体9是一种在天然免疫系统中发挥重要作用的模式识别受体,主要识别细菌和病毒DNA中的CpG基序,活化信号通路,诱导产生强烈的Th1优势免疫应答,调节IFN-α、ILs等细胞因子的分泌,参与感染和过敏性疾病、肿瘤、自身免疫性疾病的发病... Toll样受体9是一种在天然免疫系统中发挥重要作用的模式识别受体,主要识别细菌和病毒DNA中的CpG基序,活化信号通路,诱导产生强烈的Th1优势免疫应答,调节IFN-α、ILs等细胞因子的分泌,参与感染和过敏性疾病、肿瘤、自身免疫性疾病的发病。因此,靶向TLR9的药物在这些疾病的治疗中有广泛的应用前景。 展开更多
关键词 TOLL样受体9 CpG—DNA tlr9激动剂 tlr9拮抗剂 免疫治疗
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