{"title":"瘦蛋白/多糖处理的树突状细胞疫苗改善了癌症动物模型中的细胞免疫反应。","authors":"Pedram Basirjafar, Raziyeh Zandvakili, Javad Masoumi, Nahid Zainodini, Zahra Taghipour, Hossein Khorramdelazad, Soheila Yousefi, Tayyebeh Tavakoli, Mahboobeh Vatanparast, Sepehr Safdel, Mahsa Gheitasi, Fatemeh Ayoobi, Bahar Naseri, Abdollah Jafarzadeh","doi":"10.1080/08923973.2023.2253989","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers.</p><p><strong>Materials and methods: </strong>Tumors were established in mice by subcutaneously injecting 7 × 10<sup>5</sup> 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-β) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively.</p><p><strong>Results: </strong>Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (<i>p</i> = .0002), increasing survival rate (<i>p</i> = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (<i>p</i> < .001) and TH1 cells (<i>p</i> < .01); promoted the production of IFN-γ (<i>p</i> < .0001) and IL-12 (<i>p</i> < .001) by splenocytes; enhanced the T-bet (<i>p</i> < .05) and Granzyme B (<i>p</i> < .001) expression, whereas decreased the TGF-β and FOXP3 expression (<i>p</i> < .05).</p><p><strong>Conclusion: </strong>Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.\",\"authors\":\"Pedram Basirjafar, Raziyeh Zandvakili, Javad Masoumi, Nahid Zainodini, Zahra Taghipour, Hossein Khorramdelazad, Soheila Yousefi, Tayyebeh Tavakoli, Mahboobeh Vatanparast, Sepehr Safdel, Mahsa Gheitasi, Fatemeh Ayoobi, Bahar Naseri, Abdollah Jafarzadeh\",\"doi\":\"10.1080/08923973.2023.2253989\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers.</p><p><strong>Materials and methods: </strong>Tumors were established in mice by subcutaneously injecting 7 × 10<sup>5</sup> 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-β) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively.</p><p><strong>Results: </strong>Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (<i>p</i> = .0002), increasing survival rate (<i>p</i> = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (<i>p</i> < .001) and TH1 cells (<i>p</i> < .01); promoted the production of IFN-γ (<i>p</i> < .0001) and IL-12 (<i>p</i> < .001) by splenocytes; enhanced the T-bet (<i>p</i> < .05) and Granzyme B (<i>p</i> < .001) expression, whereas decreased the TGF-β and FOXP3 expression (<i>p</i> < .05).</p><p><strong>Conclusion: </strong>Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.</p>\",\"PeriodicalId\":13420,\"journal\":{\"name\":\"Immunopharmacology and Immunotoxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunopharmacology and Immunotoxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/08923973.2023.2253989\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunopharmacology and Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08923973.2023.2253989","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：在树突状细胞（DC）中，瘦素作为一种免疫调节激素，增加IL-12的产生，而减少IL-10的产生，从而促进TH1细胞的分化。使用癌症（BC）小鼠模型，我们评估了瘦蛋白和/或脂多糖（LPS）处理的DC疫苗对各种T细胞相关免疫标志物的影响。材料和方法：通过皮下注射7 × 105个4T1细胞插入右翼。小鼠在肿瘤诱导后第12天和第19天接受用Leptin、LPS和Leptin/LPS预处理的DC疫苗。在第26天处死动物，之后测定脾脏细胞毒性T淋巴细胞（CTL）和TH1细胞的频率；分别用流式细胞术、ELISA和实时PCR方法检测肿瘤裂解物刺激的脾细胞产生干扰素-γ（IFN-γ）、白细胞介素12（IL-12）和肿瘤生长因子β（TGF-β），以及肿瘤中T-bet、FOXP3和颗粒酶B的mRNA表达。结果：Leptin/LPS处理的mDC组对肿瘤生长的抑制作用更强（p = .0002），提高存活率（p = .001），并与未经治疗的荷瘤小鼠（UT对照）相比预防转移。与UT对照组相比，Leptin/LPS处理的mDC也显著增加了CTL的脾脏频率（p p p p p p p 结论：与Leptin和LPS处理的mDC疫苗相比，Leptin/LPS处理的m DC疫苗在抑制BC发育和增强抗肿瘤免疫反应方面更有效。
Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.
Purpose: In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers.
Materials and methods: Tumors were established in mice by subcutaneously injecting 7 × 105 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-β) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively.
Results: Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (p = .0002), increasing survival rate (p = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (p < .001) and TH1 cells (p < .01); promoted the production of IFN-γ (p < .0001) and IL-12 (p < .001) by splenocytes; enhanced the T-bet (p < .05) and Granzyme B (p < .001) expression, whereas decreased the TGF-β and FOXP3 expression (p < .05).
Conclusion: Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.
期刊介绍：
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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