ACS Applied Materials & Interfaces
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2025
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IF 8.2
Zhen-Ming Lu,Zi-Wen Qiu,Yan-Mei Li,Ke-Yan Zhang,Ye-Yang Wu,Ni Yan,Hong Cheng
Breast cancer cells are characterized by heightened autophagy, which impairs tumor-associated antigen presentation and represents a significant barrier to the antitumor immunity. In this study, a PD-L1-targeting autophagy modulator (PFC@CQ) is fabricated to activate the photoimmunotherapy against breast cancer. Specifically, the hydrophobic photosensitizer protoporphyrin IX (PpIX) is covalently linked to the hydrophobic peptide FFVLK and a PD-L1-targeting peptide sequence CLQKTPKQC, resulting in the formation of an amphiphilic photosensitizer-peptide conjugate (PpIX-FFVLK-CLQKTPKQC, called PFC), which is capable of encapsulating the autophagy inhibitor chloroquine (CQ). PFC@CQ can not only facilitate the targeted drug codelivery to PD-L1-overexpressing breast cancer cells, but also effectively disrupt their immune evasion by blocking PD-1/PD-L1 pathway. Upon light irradiation, the photodynamic therapy (PDT) of PFC@CQ induces tumor cell destruction and immunogenic cell death (ICD), causing the release of damage-associated molecular patterns (DAMPs). Simultaneously, PFC@CQ can inhibit autophagy pathway to mediate the upregulation of MHC-I, thereby enhancing antigen presentation. This cascade immunomodulation promotes the dendritic cell maturation and CD8+ T cell activation, leading to a synergistic suppression of both primary and metastatic tumors. This work introduces an innovative autophagy modulation strategy with potent immunomodulatory capability, demonstrating a potential to trigger systemic antitumor immune responses through local treatment.
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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DOI
PubMed
高影响因子
Frontiers in Immunology
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2025
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IF 5.9
Huimin Xie,Lin Ma,Xiaoli He,Songsong Zhao,Jin Wang,Ao Zhu,Changming Liu,Olga Piskareva,Chao Deng,Fenghua Meng,Mi Liu
Introduction: Cancer vaccines work through activating tumor-specific T cells, which can specifically attack cancer cells by recognizing antigens binding with Major-Histocompatibility-Complex I (MHC I) molecules. The downregulation or loss of MHC I expression on tumor cells can affect the efficacy of cancer vaccines.Methods: Herein, to increase the MHC I expression on tumor cells, a nanovesicle-based strategy was developed to improve the efficacy of cancer vaccines. Several clinically applied medicines, such as tyrosine kinase inhibitors (TKIs), were screened for their capacity to upregulate MHC I.Results: Two TKIs, Sunitinib and Sorafenib, were found to be very effective in elevating MHC I expression, and they were encapsulated into redox-responsive nanovesicles respectively (SUN-KD10 or SOR-KD10), which demonstrated favourable tumor-targeting capabilities in the tumor microenvironment. Sunitinib or Sorafenib activates the IFNγ/STAT1 pathway, which improve the expression of MHC I. When combined with whole-tumor-antigen-loaded nanovaccines, these nanovesicle formulations elicited a synergistic antitumor effect in both breast cancer and melanoma mouse models. The tumors in the tumor-bearing mice treated with combined strategy grew more slowly and the survival times of such mice are significantly prolonged.Discussion: The studies demonstrated that more tumor-specific T cells were activated in the combined strategy treated mice, suggesting improved immune-mediated tumor clearance. This combinatorial approach provides a promising strategy to overcome immune evasion and to enhance the therapeutic outcomes of cancer vaccine-based immunotherapy by using clinical-applied medicines with cancer vaccines.
研究领域:
肿瘤学
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免疫学
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纳米技术
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药理学
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分子生物学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Mengyue Pei,Rong Xu,Chuangnian Zhang,Xiaoli Wang,Chen Li,Yunzhang Hu
Cancer immunotherapy is an important tumor therapy option for prevention and treatment of tumors and has attracted tremendous interests. However, the therapeutic outcomes are limited by insufficient antigen uptake and presentation by antigen-presenting cells such as dendritic cells (DCs). In this study, mannose-functionalized antigen nanoparticles with endosome escape activity were designed for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy. Mannose was selected as DCs targeting ligand to enhance antigen uptake. Model antigen ovalbumin (OVA) was directly conjugated with mannose to obtain DCs targeting antigen, which was then complexed with polyethylenimine (PEI) through electrostatic interaction to form mannose-functionalized antigen nanoparticles (MAN-OVA/PEI NPs). Flow cytometry analysis revealed that the MAN-OVA/PEI NPs greatly increased antigen uptake by DCs compared with OVA/PEI NPs. Confocal laser scanning microscopy further demonstrated that MAN-OVA/PEI NPs enhanced cytosolic antigen release. Moreover, MAN-OVA/PEI NPs significantly promoted cytokine production and DCs maturation in vitro . More importantly, MAN-OVA/PEI NPs treated DCs exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro . This work suggests that mannose-functionalized antigen nanoparticles provide a versatile delivery vehicle for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy.
研究领域:
癌症免疫治疗
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纳米技术
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免疫学
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药学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR CELL
·
2019
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IF 14.548
Peng Wu,Tongtong Zhang,Baoyu Liu,Panyu Fei,Lei Cui,Rui Qin,Huaying Zhu,Danmei Yao,Ryan J. Martinez,Wei Hu,Chenyi An,Yong Zhang,Junwei Liu,Jiawei Shi,Juan Fan,Weiwei Yin,Jie Sun,Chun Zhou,Xun Zeng,Chenqi Xu,Jianan Wang,Brian D. Evavold,Cheng Zhu,Wei Chen,Jizhong Lou
Summary TCRs recognize cognate pMHCs to initiate T cell signaling and adaptive immunity. Mechanical force strengthens TCR-pMHC interactions to elicit agonist-specific catch bonds to trigger TCR signaling, but the underlying dynamic structural mechanism is unclear. We combined steered molecular dynamics (SMD) simulation, single-molecule biophysical approaches, and functional assays to collectively demonstrate that mechanical force induces conformational changes in pMHCs to enhance pre-existing contacts and activates new interactions at the TCR-pMHC binding interface to resist bond dissociation under force, resulting in TCR-pMHC catch bonds and T cell activation. Intriguingly, cancer-associated somatic mutations in HLA-A2 that may restrict these conformational changes suppressed TCR-pMHC catch bonds. Structural analysis also indicated that HLA polymorphism might alter the equilibrium of these conformational changes. Our findings not only reveal critical roles of force-induced conformational changes in pMHCs for activating TCR-pMHC catch bonds but also have implications for T cell-based immunotherapy.
研究领域:
免疫学
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生物物理学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Water Process Engineering
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2023
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IF 7
Chuxuan Zhang,Jianhui Zeng,Zhipeng Ouyang,Xiaomin Li,Luqiu Lin,Yang Peng,Xun Gong
Efficient and economical catalysts are crucial for activating H 2 O 2 in Fenton-like reactions. Microalgae harvesting by magnetic separation will inevitably result in unrecovered Fe 3 O 4 nanoparticles (Fe 3 O 4 NPs) entering the downstream oil production stage. This part of Fe 3 O 4 NPs can play a catalytic role in the co-liquefaction process with microalgae to improve the bio-oil quality, and then be separated from the liquid phase along with microalgae hydrochar (MHC). Herein, this N-rich MHC loaded Fe 3 O 4 NPs composite (Fe 3 O 4 @MHC) as a by-product was recycled without reprocessing to remove Rhodamine B (RhB). Detailed characterization data indicates that Fe 3 O 4 NPs can be well anchored and dispersed on MHC surface after liquefaction . The Fe 3 O 4 @MHC exhibits an outstanding catalytic performance in the activation of H 2 O 2 for RhB degradation, with a removal rate of >97 % within 60 min at a lower dosage (0.17 g/L). MHC act as electron donors due to the abundant oxygen- and nitrogen-containing functional groups to accelerate Fe 2+ /Fe 3+ cycle. OH and O 2 − are the dominant active species in catalytic systems. This study not only provides an economical carbon material with high efficiency for environmental remediation, but also proposes a reliable solution for the disposal of solid residues after microalgae bio-oil production.
研究领域:
环境科学
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催化
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废水处理
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生物技术
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产品关联
DOI
高影响因子
Journal for ImmunoTherapy of Cancer
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2025
·Vol. 13
·期 9
·e011893
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IF 10.6
Zhengning Yang,Zhongxuan Meng,Shangyuan Liu,Yuxin Chen,Xuhong Gan,Zi‑Mei Zhang,Xiaoshan Luo,Jiahong Yan,Huijin Chen,Danqing Huang,Lihong Huang,Xiaomin Zeng,Wenyu Ma,Jun Liu,Linlin Wang,Haotian Huang,Xinyi Yang,Mei Hu,Lin Chen,Hongli Du,Qibin Leng,Li Qiu,Xiaoling Wang
Background Nonsense-mediated messenger RNA decay (NMD) is a highly conserved surveillance system that degrades mRNAs with premature termination codons (PTCs), and regulates the mRNA quantity. Cancer cells hijack NMD to compensate for the imbalanced DNA levels and modulate their antigenicity. We identified the LTO1/YAE1 complex as NMD factors regulating ribosome biogenesis. Our study aimed to investigate their roles in modulating NMD and major histocompatibility complex class I (MHC-I) antigen presentation, which is vital for cancer immunotherapy. Methods Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9)-mediated gene knockouts, overexpression, and mutational analysis were used to explore the role of LTO1 and YAE1 in NMD and MHC-I expression across various tumor cell lines, assayed by fluorescent reporter-based assays, fluorescence-activated cell sorting analysis, reverse transcription-quantitative PCR, mRNA decay assay, and polysome profiling. Transcriptomic analyses were used to assess the expression of LTO1/YAE1 and their correlation with MHC-I molecules in human cancers. T cell receptor (TCR)-T cells and tumor cells coculture were employed to monitor the effect of LTO1 and YAE1 loss on T cell activation. Iron chelators were further tested as NMD inhibitors to enhance cancer immunotherapy using in vitro coculture assay and a mouse tumor model for immune checkpoint blockade (ICB) therapy. Results We demonstrate that deficiency in LTO1, YAE1, or their downstream target ABCE1 impairs NMD, causes the overexpression of key regulators of MHC-I, including NLR family CARD domain containing 5 (NLRC5), interferon regulatory factor 1 (IRF1), and nuclear factor-kappa B (NFκB), which results in enhanced T cell activation and tumor cell killing in TCR-T models. Transcriptomic analyses reveal that the LTO1/YAE1 complex is frequently overexpressed in human cancers, where it negatively regulates MHC-I. Moreover, low doses of iron chelators inhibit NMD and enhance MHC-I expression, leading to improved recognition and activation of CD8 + T cells, thereby promoting antigen-specific killing and increasing the efficacy of TCR-T and ICB therapy. Conclusions Collectively, our findings establish novel roles for the LTO1/YAE1 complex in regulating MHC-I expression via NMD. As MHC-I is crucial for antigen presentation and T cell activation, these results reveal a previously unappreciated link between NMD and tumor immunogenicity, with potential implications for cancer immunotherapies.
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
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IF 5.6
Shihui Wang,Qing Xu,Xueqian Peng,Xinman Li,Tianqing Zheng
Conventional CD3-targeting bispecific T cell engagers (BiTEs) have shown limited efficacy in solid tumors, largely due to the highly immunosuppressive tumor microenvironment (TME) and systemic T cell activation-associated toxicity. To address this challenge, we developed a peptide–MHC class I-based T cell engager platform that selectively redirects a specific subset of CD8 + T cells to tumor cells. Using the model ovalbumin (OVA) system, we engineered fusion proteins comprising an OVA peptide–H-2Kᵇ complex linked to an anti-HER2 nanobody (OVA-αHER2), enabling simultaneous engagement of OVA-specific T cells and HER2-expressing tumor cells and inducing potent tumor cell killing in vitro . To overcome the immunosuppressive TME, we further combined a HER2-targeted IL-12 fusion protein with OVA-αHER2, achieving synergistic anti-tumor responses in a mouse B16-HER2 solid tumor model. This treatment enhanced both systemic and intratumoral OVA-specific CD8 + T cell responses, accompanied by increased IFN-γ production in the TME. Together, these findings establish a modular immunotherapy strategy that integrates recruitment of a specific CD8 + T cell subset with localized cytokine-mediated immune reprogramming, providing a potential approach for HER2-positive solid tumors.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 11
Shanlingzi Huang,Lu Gao,Yujun Chen,Zhaoming Fu,Ziyou Wang,Yifan Liu,Zhicheng Zhou,Ru Huang,Wen Song,Feifan Zhou
Triple-negative breast cancer (TNBC), characterized by low immunogenicity, is a challenging issue in clinical treatment due to its poor response to various therapies. The transformation of TNBC from a “cold tumor” with low immunogenicity into a “hot tumor” that elicits stronger immune responses is a key research focus. Photodynamic therapy (PDT) has emerged as a promising solution for TNBC treatment because it can effectively induce immunogenic cell death (ICD), which prompts the release of damage-associated molecular patterns (DAMPs) and activates immune responses. The role of MHC-I molecules in antigen presentation is crucial, but TNBC cells often evade immune surveillance by downregulating or losing MHC-I expression. Recent studies have shown that inhibiting the activity of complex II (CII) in the mitochondrial electron transport chain of tumor cells can promote MHC-I expression. Based on this finding, the combination of the PDT photosensitizer PCN-224 with the CII inhibitor 3-nitropropionic acid (3NPA) to form PCN@3NPA has been innovatively developed. Furthermore, modification with hyaluronic acid (HA) enables targeted delivery to TNBC cells that overexpress CD44. PDT induces ICD in tumor cells, releasing large amounts of DAMPs, while the sustained release of 3NPA effectively inhibits CII activity, significantly enhances MHC-I expression, thereby boosting tumor cell immunogenicity. This process significantly improves the recognition and killing of tumor cells by CD8 + T cells, markedly strengthening the body's anti-tumor immune response. This approach offers a novel and promising strategy for efficiently treating not only low-immunogenic TNBC but also other similar tumors, bringing new hope for future clinical treatments.
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PubMed
高影响因子
NEURON
·
2025
·
IF 15
Tao Qin,Tao Jiang,Zihan Zhou,Mengyuan Wu,Yuanzhen Zhang,Zhenqi Yang,Ziyang Zheng,Jiang Yi,Xiaowei Wang,Mingran Luo,Peng Gao,Jiayun Liu,Yifan Huang,Hao Liu,Qingqing Li,Wei Zhou,Shujun Zhang,Xiaodong Guo,Baorong He,Yongxiang Wang,Jin Fan,Shujie Zhao,Jian Chen,Guoyong Yin
The spatiotemporal dynamics and specific roles of regulatory T (Treg) cells in spinal cord injury (SCI) remain unclear. Using single-cell RNA sequencing, flow cytometry, and immunofluorescence, we found that thymus-derived Treg cells infiltrate the injured spinal cord via peripheral blood around 3 days post-SCI. Treg cell depletion worsened SCI and impaired long-term recovery. Transcriptomic profiling revealed strong anti-inflammatory functions of Treg cells and the potential to regulate cholesterol metabolism in neighboring microglia. Further single-cell RNA sequencing uncovered the clonality of SCI-associated Treg cells. Major histocompatibility complex class II (MHC II) expression on microglia, not macrophages, was crucial for sustaining Treg cell numbers and neuroprotective function, with myelin-phagocytosing microglia-activated Treg cells showing significant neuroprotective effects. Treg cells mitigated microglial inflammation via CTLA-4 and upregulated the ATP-binding cassette transporter G1 (Abcg1) receptor in microglia, helping to manage myelin load and reduce lipid droplet formation. Our findings offer mechanistic insights into SCI-associated Treg cells and lay the groundwork for future Treg-based therapies in SCI treatment.
研究领域:
免疫学
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神经科学
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分子生物学
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转化医学
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炎症与修复
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神经免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
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IF 5.4
Yuhui Ye,Xiaoyi Jiang,Yijun Jiang,Longteng Zhang,Binsong Han,Yulong Wang,Pengyan Liu,Xin Lu,Cun-Zheng Zhang
Although often regarded as compromising the fruit’s sensory quality, pear peel is an edible component that enhances the nutritional and functional value of pears within a whole food diet. Rich in diverse polyphenols with demonstrated bioactivity, the pear peel represents a valuable dietary source of health-promoting compounds, however, its role in ulcerative colitis (UC) remains underexplored. In this study, the protective effect of pear peel polyphenols (PPP) against UC was investigated using both in vitro and in vivo models. PPP markedly suppressed proinflammatory cytokine and enzyme expressions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. In dextran sulfate sodium (DSS) induced colitis mice, PPP significantly mitigated UC symptoms, suppressed serum inflammatory cytokine production, and ameliorated histological damage in colon tissues. Moreover, PPP modulated the gut microbiota by reshaping microbial diversity, enriching beneficial taxa such as Akkermansia, and suppressing proinflammatory taxa including Bacteroides, Enterobacteriaceae, and Parabacteroides. Proteomic analysis further demonstrated that PPP modulated mucosal immunity, particularly by rebalancing immunoglobulin-related processes (IgM, IgD, and IgA) and attenuating antigen presentation responses involving major histocompatibility complex (MHC) class II molecules and cluster of differentiation (Cd40) signaling. Together, these findings suggest that PPP exerts a protective effect against colitis through the coordinated regulation of gut microbiota and mucosal immunity, highlighting its potential as a functional food ingredient for intestinal health.
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Chenglong Li,Shuhao Xu,Xin Li,Huaiyu Su,Can Qian,Yingying Hou,Sanjun Shi
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, damage, and disability. Activated fibroblast-like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC-II). This upregulation facilitates their interaction with CD4 + T cells, triggering an inflammatory cascade that exacerbates synovial inflammation. To address this, a DSPE-mPEG 2000 -GPA-KLVFF-decorated liposome loaded with dexamethasone (DPGK@Lipo-Dex) is developed to precisely target FLSs in arthritic joints. DPGK@Lipo-Dex achieves efficient binding to FLSs through a specific enzymatic interaction between fibroblast activation protein-α (FAP-α) and GPA, along with prolonged retention in the joints due to the fibrillar transformation of KLVFF. In vitro studies demonstrate that DPGK@Lipo-Dex enhances cellular uptake and reduces MHC-II expression on aggressive FLSs. In adjuvant-induced arthritis (AIA) rats, DPGK@Lipo shows specific distribution patterns that target both inflamed joints and FLSs. Treatment with DPGK@Lipo-Dex leads to a downregulation of MHC-II expression, a decrease in the number of activated T cells within the synovium, and a reduction in levels of proinflammatory mediators. Overall, DPGK@Lipo-Dex effectively suppresses FLSs-related responses and ultimately results in inflammatory remission. This makes DPGK@Lipo-Dex a promising candidate for nano-therapeutic treatment in rheumatoid arthritis.
研究领域:
免疫学
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纳米医学
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风湿病学
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分子靶向治疗
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药剂学
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转化医学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Qingxia Yuan,Rongyi Liang,Kunling Lv,Xiaohuo Shi,Jing Leng,Yonghong Liu,Jian Xiao,Lifeng Zhang,Longyan Zhao
Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity. In this study, the major polysaccharide fraction, CPP-3a, in Chlorella pyrenoidosa , was isolated, and its detailed structure was investigated by analyzing the low-molecular-weight product prepared via free radical depolymerization. The results indicated that CPP-3a with a molecular weight of 195.2 kDa was formed by →2)-α-L-Ara f -(1→, →2)-α-D-Rha p -(1→, →5)-α-L-Ara f -(1→, →3)-β-D-Glc p- (1→, →4)-α-D-Glc p- (1→, →4)-α-D-Glc p A-(1→, →2,3)-α-D-Man p- (1→, →3,4)-α-D-Man p- (1→, →3,4)-β-D-Gal p- (1→, →3,6)-β-D-Gal p- (1→, and →2,3,6)-α-D-Gal p- (1→ residues, branched at C2, C3, C4, or C6 of α/β-D-Gal p and α-D-Man p , and terminated by α/β-L-Ara f , α-L-Ara p , α-D-Gal p , and β-D-Glc p . Biological assays showed that CPP-3a significantly altered the dendritic morphology of immature dendritic cells (DCs). Enhanced CD80, CD86, and MHC I expression on the cell surface and decreased phagocytic ability indicated that CPP-3a could induce the maturation of DCs. Furthermore, CPP-3a-stimulated DCs not only stimulated the proliferation of allogeneic naïve CD4 + T cells and the secretion of IFN-γ, but also directly stimulated the activation and proliferation of CD8 + T cells through cross-antigen presentation. These findings indicate that CPP-3a can promote human DC maturation and T-cell stimulation and may be a novel DC maturation inducer with potential developmental value in DC immunotherapy.
研究领域:
免疫学
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生物化学
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药理学
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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）