MEDICAL SCIENCE MONITOR
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2019
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IF 1.98
Liang Chen,Hanfei Huang,Weixin Zhang,Feifan Ding,Zhenlei Fan,Zhong Zeng
Background CD8 + cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4 + CD25 + regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4 + CD25 + Treg cells on CD8 + CTL depends on EXOs remains unknown and needs to be explored. Material/Methods We purified CD4 + CD25 + Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4 + CD25 + Treg cells and CD4 + CD25 + Treg cells-derived EXOs on CD8 + CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. Results We successfully obtained EXOs from CD4 + CD25 + Treg cells. The inhibition effect of EXOs on CD8 + CTL was concentration-dependent. In addition, the inhibition effect of CD4 + CD25 + Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4 + CD25 + Treg cells-released EXOs can prolong liver allograft survival. Conclusions CD4 + CD25 + Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.
研究领域:
免疫学
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移植医学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
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2017
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IF 8.402
Fei Duan,Xiaochen Feng,Xinjian Yang,Wentong Sun,Yi Jin,Huifang Liu,Kun Ge,Zhenhua Li,Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy . However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8 + cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm. TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds. The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation. Furthermore, the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide (CpG) through Watson−Crick base pairing would further enhance CD8 + cytotoxic T lymphocyte responses. We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple, convenient and effective and showed no obvious toxicity both in vitro and in vivo . This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55% (w/w). Additionally, the pH-responsive co-delivery system exerted enhanced antitumor outcome (about 100% survival) in B16-OVA melanoma cancers in vivo . Furthermore, we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte. This work demonstrates the ability of pH-responsive, endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens.
研究领域:
生物医学工程
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免疫学
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癌症研究
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2023
·Vol. 14
·期 2
·1-11
·
IF 9
Yao Yuan,Feng Suya,Li Xuejiao,Liu Taohua,Ye Shengying,Ma Long,Man Shuli
Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi ( Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus , and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8 + cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2024
·
IF 4.8
Li-Li Zhang,Jia-Ying Xu,Wei Wei,Zhi-Qiang Hu,Yan Zhou,Jia-Yang Zheng,Yu Sha,Lin Zhao,Jing Yang,Qi Sun,Li-Qiang Qin
Background Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. Methods The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. Results CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8 + cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Conclusions Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses.
研究领域:
放射生物学
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免疫学
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胃肠病学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Zhao Yading,Shi Dandan,Guo Lu,Shang Mengmeng,Sun Xiao,Meng Dong,Xiao Shan,Wang Xiaoxuan,Li Jie
Immunotherapy had demonstrated inspiring effects in tumor treatment, but only a minority of people could benefit owing to the hypoxic and immune-suppressed tumor microenvironment (TME). Therefore, there was an urgent need for a strategy that could relieve hypoxia and increase infiltration of tumor lymphocytes simultaneously. In this study, a novel acidity-responsive nanoscale ultrasound contrast agent (L-Arg@PTX nanodroplets) was constructed to co-deliver paclitaxel (PTX) and L-arginine (L-Arg) using the homogenization/emulsification method. The L-Arg@PTX nanodroplets with uniform size of about 300 nm and high drug loading efficiency displayed good ultrasound diagnostic imaging capability, improved tumor aggregation and achieved ultrasound-triggered drug release, which could prevent the premature leakage of drugs and thus improve biosafety. More critically, L-Arg@PTX nanodroplets in combination with ultrasound targeted microbubble destruction (UTMD) could increase cellular reactive oxygen species (ROS), which exerted an oxidizing effect that converted L-Arg into nitric oxide (NO), thus alleviating hypoxia, sensitizing chemotherapy and increasing the CD8 + cytotoxic T lymphocytes (CTLs) infiltration. Combined with the chemotherapeutic drug PTX-induced immunogenic cell death (ICD), this promising strategy could enhance immunotherapy synergistically and realize powerful tumor treatment effect. Taken together, L-Arg@PTX nanodroplets was a very hopeful vehicle that integrated drug delivery, diagnostic imaging, and chemoimmunotherapy.Graphical Abstract
研究领域:
肿瘤学
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药学
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生物医学工程
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
·
IF 4.845
Yi Chen,Qianming Du,Ying Zou,Qianqian Guo,Jing Huang,Ling Tao,Xiangchun Shen,Jianqing Peng
High metastasis is responsible for the failure in the treatment of melanoma . Chemoimmunotherapy has shown conspicuous inhibition effects not only on the growth of tumor in situ, but also on the metastasis to distant organs. Given that the indoleamine-2,3 dioxygenase (IDO) overexpressed in the microenvironment of tumor leads to the immune escape, the combination of chemotherapeutic drug and IDO inhibitor might be a promising chemoimmunotherapy. Besides, the hematogenous metastasis mediated by platelets was supposed to be blocked by the heparin (HP). Therefore, a drug delivery system with all these elements involved might be a potential treatment for melanoma. Here, we developed a pH-sensitive liposomal dual-delivery system for doxorubicin (DOX) and epacadostat (EPA) with HP coated (HP/LDE). It was confirmed to enhance cytotoxicity and apoptosis , reverse the platelets-activated epithelial mesenchymal transformation (EMT) and prevent the invasion and migration in vitro . After systemic administration , HP/LDE provided the optimum anti-metastasis effect on the melanoma. The results of evaluation on DC maturation, CD8 + cytotoxic T lymphocytes (CTLs) activation and T cell mediated cytotoxicity were consistent in vitro and in vivo . Taken together, our study established a functional liposomal dual-delivery system with ideal anti-metastasis efficacy on melanoma.
研究领域:
肿瘤学
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药理学
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免疫学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）