The lactate receptor HCAR1 drives the recruitment of immunosuppressive PMN-MDSCs in colorectal cancer

Nature Immunology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

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Platinum(IV) Complexes Trigger Death Receptors and Natural Killer Cells to Suppress Breast Cancer

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Chemoimmunotherapy is an alternative treatment against cancers. Platinum(IV) complexes FMP and DFMP, coupling formononetin derivative as axial ligand(s), were designed to suppress triple-negative breast cancer (TNBC) by activating death receptors (DRs) natural killer (NK) cells. These show great potential overcome the resistance of TNBC chemotherapy inducing both intrinsic extrinsic apoptosis in Particularly, with one not only induced caspase-3-dependent but also upregulated expression DRs caspase-8, triggered apoptosis, enhanced cytotoxic ability NK92 Moreover, increased release granzyme B, restrained proliferation differentiation myeloid-derived suppressor cells, secretion IL-10, thus inhibiting vitro vivo. The results demonstrate that overcomes chemoresistance immune escape through a new mechanism involving synergy immunotherapy.

Язык: Английский

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Myeloid-derived suppressor cells in metabolic and cardiovascular disorders

Trends in Endocrinology and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Deciphering the Preeclampsia-Specific Immune Microenvironment: The Role of Pro-inflammatory Macrophages

Опубликована: Март 4, 2025

Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, comprehensive understanding the immune microenvironment in placenta PE differences between GDM still lacking. In this study, Cytometry time flight (CyTOF) indicated that frequencies memory-like Th17 cells (CD45RA - CCR7 + IL-17A CD4 ), CD8 T (CD38 CXCR3 Helios CD127 ) pro-inflam Macs (CD206 CD163 CD38 mid CD107a low CD86 HLA-DR CD14 were increased, while anti-inflam CD33 granulocyte myeloid-derived suppressor (gMDSCs, CD11b CD15 hi decreased compared NP, but not or GDM&PE. The positively correlated negatively gMDSCs. Single-cell RNA sequencing revealed transferring F4/80 CD206 Folr2 Ccl7 Ccl8 C1qa C1qb C1qc phenotype from uterus mice to normal pregnant induced production IL-17a Rora Il1r1 TNF Cxcr6 S100a4 CD44 via IGF1-IGF1R, which contributed development recurrence PE. Pro-inflam also inhibited Ly6g S100a8 S100a9 Retnlg Wfdc21 gMDSCs at maternal-fetal interface, leading PE-like symptoms mice. conclusion, study PE-specific cell network, was regulated Macs, providing new ideas about pathogenesis

Язык: Английский

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Systemic EP4 receptor agonist and Arginase‐1 therapy in a murine model of chronic asthma and influenza virus‐induced asthma exacerbation

British Journal of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Background and Purpose Myeloid‐derived suppressor cells (MDSCs) play important roles in the pathogenesis of asthma. Recent studies demonstrate that their function can be modulated by different pharmacological approaches. In this study, we focussed on effects systemically administered prostaglandin EP 4 receptor agonist L‐902,688 pegylated human Arginase‐1 MDSCs a murine model chronic asthma exacerbation. Experimental Approach BALB/c mice were challenged with house dust mite (HDM) over period 5 weeks, establishing phenotype. To induce exacerbation, infected Influenza Virus H1N1 A/Puerto Rico/8/1934. vivo lung function, inflammatory features, number suppressive activity MDSCs, T cell subsets spleen viral titer bronchoalveolar lavage fluid (BALF) assessed. Key Results asthmatic mice, treatment or significantly reduced eosinophils BALF. Both treatments improved ameliorated airway hyperresponsiveness (AHR) The increased virus‐induced Conclusion Implications We found beneficial systemic therapy influenza Our findings highlight potential efficacy agonists, Arginase‐1, as novel therapeutic approaches

Язык: Английский

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Intrapulmonary-administered myeloid derived suppressor cells rescue mice from Pseudomonas aeruginosa infection and promote a regulatory/repair phenotype

Mucosal Immunology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Pseudomonas aeruginosa (P.aeruginosa) is a pathogenic opportunistic bacterium, classified as priority by the WHO for research of new treatments. As this bacterium harmful through inflammation and tissue damage it causes, we investigated role Myeloid Derived Suppressor Cells (MDSC) in P.aeruginosa infections their potential therapeutic tool. Using both 'classically' obtained MDSC (through mice bone-marrow differentiation), procedure developed here (using ER-Hoxb8 hematopoietic cell line), observed that after administering intra-nasally lethal dose (PAO1), intra-pulmonary transfer MDSC, prophylactic protocols, markedly improves survival infected animals. Mechanistically, with sub-lethal P.aeruginosa, modulated lung injury, down-regulated inflammatory responses elicited repair. We further showed WT-PAO1 (and subtypes PMN-MDSC M-MCSF) could interact directly vitro vivo, PMN- M-MDSC gene expression (assessed RNA sequencing) was infection, (but not ΔFlic-PAO1) infection led to inhibition T proliferation promoted epithelial wound healing. Furthermore, transcription factor Nr4A1 up-regulated M-MDSC- cells may be an important mediator process. Altogether, highlight beneficial suggest unique properties make them attractive tools patients acute or chronic diseases.

Язык: Английский

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Contemporary understanding of myeloid-derived suppressor cells in the acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) tumor microenvironment

Expert Review of Anticancer Therapy, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Март 23, 2025

Introduction Myeloid-derived suppressor cells (MDSCs) are a key immunosuppressive component in the tumor microenvironment, contributing to immune evasion and disease progression acute myeloid leukemia (AML) myelodysplastic syndromes (MDS).

Язык: Английский

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MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy

Cancer Gene Therapy, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Despite the success of cancer immunotherapy in treating hematologic malignancies, their efficacy solid tumors remains limited due to immunosuppressive tumor microenvironment (TME), which is mainly formed by myeloid-derived suppressor cells (MDSCs). MDSCs not only exert potent effects that hinder immune checkpoint inhibitors (ICIs) and adaptive cellular therapies, but they also promote advancement through non-immunological pathways, including promoting angiogenesis, driving epithelial-mesenchymal transition (EMT), contributing establishment pre-metastatic environments. While targeting alone or combination with conventional therapies has shown success, emerging evidence suggests MDSC blockade other immunotherapies holds great promise overcoming both immunological barriers. In this review, we discussed dual roles MDSCs, a particular emphasis on underexplored checkpoints strategies. We rationale behind strategies, potential advantages MDSC-mediated immunosuppression, challenges associated development. Additionally, highlight future research directions aimed at optimizing enhance therapeutic effectiveness, particularly where are highly prevalent.

Язык: Английский

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Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface

eLife, Год журнала: 2025, Номер 13

Опубликована: Март 28, 2025

Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, comprehensive understanding the immune microenvironment in placenta PE differences between GDM still lacking. In this study, cytometry time flight indicated that frequencies memory-like Th17 cells (CD45RA − CCR7 + IL-17A CD4 ), CD8 T (CD38 CXCR3 Helios CD127 ) pro-inflam Macs (CD206 CD163 CD38 mid CD107a low CD86 HLA-DR CD14 were increased, while anti-inflam CD33 granulocyte myeloid-derived suppressor (gMDSCs, CD11b CD15 hi decreased compared normal pregnancy (NP), but not or GDM&PE. The positively correlated negatively gMDSCs. Single-cell RNA sequencing revealed transferring F4/80 CD206 Folr2 Ccl7 Ccl8 C1qa C1qb C1qc phenotype from uterus mice to pregnant induced production IL-17a Rora Il1r1 TNF Cxcr6 S100a4 CD44 via IGF1–IGF1R, which contributed development recurrence PE. Pro-inflam also inhibited Ly6g S100a8 S100a9 Retnlg Wfdc21 gMDSCs at maternal–fetal interface, leading PE-like symptoms mice. conclusion, study PE-specific cell network, was regulated Macs, providing new ideas about pathogenesis

Язык: Английский

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Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies

Exploration of Targeted Anti-tumor Therapy, Год журнала: 2025, Номер 6

Опубликована: Март 31, 2025

Bladder cancer (BC) is a heterogeneous disease associated with high mortality if not diagnosed early. BC classified into non-muscle-invasive (NMIBC) and muscle-invasive (MIBC), MIBC linked to poor systemic therapy response recurrence rates. Current treatments include transurethral resection Bacillus Calmette-Guérin (BCG) for NMIBC radical cystectomy chemotherapy and/or immunotherapy MIBC. The tumor microenvironment (TME) plays critical role in progression, metastasis, therapeutic efficacy. A comprehensive understanding of the TME’s complex interactions holds substantial translational significance developing innovative treatments. TME can contribute resistance, particularly immune checkpoint inhibitor (ICI) therapies, where resistance arises from tumor-intrinsic changes or extrinsic factors. Recent advancements highlight importance research address these challenges. Strategies overcome focus on remodeling transform immunologically “cold” tumors, which lack cell infiltration, “hot” tumors that respond better immunotherapy. These strategies involve disrupting cancer-microenvironment interactions, inhibiting angiogenesis, modulating components enhance anti-tumor responses. Key mechanisms cytokine involvement [e.g., interleukin-6 (IL-6)], phenotypic alterations macrophages natural killer (NK) cells, plasticity cancer-associated fibroblasts (CAFs). Identifying potential targets within improve outcomes patients. This review emphasizes complexity its impact guiding novel approaches, offering hope survival

Язык: Английский

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