Small
·
2024
·
IF 13
Jiabao Dong,Xupeng Chai,Yucheng Xue,Shiyun Shen,Zhuo Chen,Zetao Wang,Eloy Yinwang,Shengdong Wang,Liang Chen,Fengfeng Wu,Hengyuan Li,Zehao Chen,Jianbin Xu,Zhaoming Ye,Xiongfeng Li,Qian Lu
Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.
研究领域:
癌症生物学
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药学
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2018
·Vol. 109
·期 9
·2677-2686
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IF 4.372
Yilin Zhao,Qi Shao,Haitao Zhu,Haiyuan Xu,Wei Long,Bin Yu,Lining Zhou,Huaxi Xu,Yan Wu,Zhaoliang Su
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells which consist of 2 subsets: granulocytic MDSC (G-MDSC) and monocytic MDSC (M-MDSC). MDSC expand in tumor-bearing hosts and contribute to immunotherapeutic resistance by remarkably blocking effector T-cell activation via different mechanisms. Resveratrol (RSV) is a polyphenol and it has been widely used for its various health benefits. However, the underlying mechanism of its anti-tumor properties remains unclear. In this study, a transplantable mouse model was used to investigate the effects of RSV on MDSC. The results showed that RSV ameliorated tumor development by decreasing G-MDSC accumulation, impairing its suppressive ability on CD8 + T cells and promoting M-MDSC differentiation into CD11c + and F4/80 + cells. Our results indicated that RSV should be considered as a modular of MDSC suppressive function and that RSV is a novel booster for tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
·
IF 8.786
Zhang Nan,Gao Xiaochen,Zhang Weijia,Xiong Junyao,Cao Xiaojian,Fu Zhen F.,Cui Min
Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).
研究领域:
免疫学
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神经病毒学
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病毒学
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致病机制
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 10
·2106682
·
IF 32.086
Xing Lai,Xue-Liang Liu,Hong Pan,Mao-Hua Zhu,Mei Long,Yihang Yuan,Zhong Zhang,Xiao Dong,Qin Lu,Peng Sun,Jonathan F. Lovell,Hong-Zhuan Chen,Chao Fang
In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme- or acid-dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light-triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)-loaded small-sized polymeric nanoparticles (DOX-NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near-infrared light-induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid-derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small-sized DOX-NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune-related assay indicates therapeutic immune enhancement. This light-triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.
研究领域:
癌症治疗
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纳米技术
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药学
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免疫学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Quanjuan Guo,Ailu Yang,Rongrong Zhao,Huajun Zhao,Yongliang Mu,Jian Zhang,Qiuju Han,Yuhang Su
Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4 + T and CD8 + T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4 + /CD8 + T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro . Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
iScience
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2024
·
IF 4.6
Junyang Li,Bingjie Mei,Lu Feng,Xiaoxin Wang,Dengfeng Wang,Jianming Huang,Guonan Zhang
Reprogramming tryptophan metabolism (TRP) may be able to overcome immunosuppression and restore the immune checkpoint blockade (ICB) response in epithelial ovarian cancer (EOC) patients resistant to ICB therapy. Because TRP metabolism is involved in the kynurenine/indole and serotonin pathways of tryptophan metabolism. Herein, employing amitriptyline (AMI), an antagonist of TLR4 and serotonin transporter (SERT), we revealed that AMI remodels the immunological landscape of EOC. In particular, AMI lowered the expression of IDO1, IL-4I1 and PD-L1, the quantity of KYN and indoles, and the level of immunosuppressive immune cells MDSC, Tregs and CD8+CD39+/PD-1+ T cell. AMI boosted the killing potential of anti-PD-1-directed CD8+T cells and worked in concert with PD-1 inhibitor to suppress tumor growth and to prolong the survival of EOC-bearing mice. This work highlights AMI as an effective regulator of ICB response by manipulating EOC cell TRP metabolism, indicating it could be a potential strategy for improving EOC ICB therapy.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Lan Zhou,Liu Wei-Jia,Yin Wu-Wei,Yang Sheng-Ren,Cui Hao,Zou Ke-Long,Cheng Guo-Wang,Chen Hao,Han Yan-Hua,Rao Lang,Tian Rui,Li Ling-Ling,Zhao Yu-Yue,Yu Guang-Tao
Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.
研究领域:
癌症研究
·
纳米技术
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免疫治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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