CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(4), P. 374 - 392

Published: Feb. 21, 2024

CD4

Language: Английский

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STING activation and overcoming the challenges associated with STING agonists using ADC (antibody-drug conjugate) and other delivery systems

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111647 - 111647

Published: Feb. 1, 2025

Language: Английский

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Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives

Materials Today Bio, Journal Year: 2023, Volume and Issue: 23, P. 100839 - 100839

Published: Oct. 21, 2023

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field cancer immunotherapy, owing to their excellent capacity activate innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration strategies employed develop effective formulations for agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements delivery systems based lipids, natural/synthetic polymers, proteins are summarized. preparation methodologies nanoprecipitation, self-assembly, hydrogel, along advantages disadvantages, also discussed. Furthermore, challenges opportunities developing next-generation agonist elaborated. aims serve reference researchers designing novel immunotherapy.

Language: Английский

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Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1286 - 1300.e8

Published: June 27, 2024

Language: Английский

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Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(1), P. e008386 - e008386

Published: Jan. 1, 2024

Background Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated local systemic immunological effects of potential combining programmed death protein 1 (PD-1) blockade to boost immunotherapy efficacy Methods We first induced by early-stage Subsequently, explored cryoablation-induced antitumor immunity underlying biological mechanisms using KP ( Kras G12D/+ , Tp53 −/− ) mutant allograft mouse models. Moreover, synergistic PD-1 was both models unresectable Results found that significantly increased circulating CD8 + T subpopulations proinflammatory cytokines models, demonstrated resulted growth inhibition contralateral, non-ablated tumors. Integrated analysis bulk, single-cell RNA receptor (TCR) sequencing data revealed reprogrammed intratumoral microenvironment infiltration higher effector signature, interferon (IFN) response, cytolytic activity. Mechanistically, promoted effect through STING-dependent type I IFN signaling pathway, attenuated effect. also combination further inhibited tumor compared either treatment alone an model. therapy notable suppression Conclusions Our results provide mechanistic insights into triggers cancer, thereby potentiating ligand (PD-L1)/PD-1 clinical

Language: Английский

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SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 14, 2024

The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators cytokine signaling. SOCS1 is the prototypical member SOCS and functions in a classic negative-feedback loop to inhibit signaling response interferon, interleukin-12 interleukin-2 cytokines. These cytokines have critical role orchestrating our immune defence against viral pathogens cancer. ability limit positions it as an checkpoint, evidenced by detection detrimental variants patients with cytokine-driven inflammatory autoimmune disease. has also emerged key checkpoint that restricts anti-tumor immunity, playing both tumor intrinsic impacting various cells mount effective response. In this review, we describe mechanism action, focusing on autoimmunity cancer, discuss potential for new SOCS1-directed cancer therapies could be used enhance adoptive immunotherapy blockade.

Language: Английский

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The complexity of immune evasion mechanisms throughout the metastatic cascade

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1793 - 1808

Published: Sept. 16, 2024

Language: Английский

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NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 18, 2024

Abstract Interactions of tumor cells with immune in the microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited development by suppressing proliferation non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing for cell-derived regulating microenvironment. positively coordinated infiltration macrophages and T NSCLC clinically, overexpression promoted recruitment both vitro vivo. Mechanistically, stabilized p53 directly binding to MYBBP1A facilitating MYBBP1A-p53 interaction, enhanced p53-mediated transcription IRF1, which activated type I interferon signaling increased production downstream CXCL10 CCL5. also found activation was associated better immunotherapy efficacy NSCLC. Furthermore, stability regulated NAT10, key enzyme responsible N4-acetylcytidine (ac4C) modification, bound mediated its ac4C modification. Collectively, could activate via MYBBP1A-p53/IRF1 axis, promoting potentially correlating efficacy, suppressed Our results suggested as promising predictive marker potential therapeutic target combination therapy

Language: Английский

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Integrated single-cell and bulk transcriptome analysis of R-loop score-based signature with regard to immune microenvironment, lipid metabolism and prognosis in HCC

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Hepatocellular carcinoma (HCC) is one of the most prevalent causes cancer-related morbidity and mortality worldwide. Late-stage detection complex molecular mechanisms driving tumor progression contribute significantly to its poor prognosis. Dysregulated R-loops, three-stranded nucleic acid structures associated with genome instability, play a key role in malignant characteristics various tumors. However, detailed mechanism R-loops HCC remain elusive require further exploration. This study aimed construct an R-loop scoring signature centered on prognosis lipid metabolism, thereby enhancing our understanding identifying potential therapeutic targets. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) data from patients (GSE149614 CRA002308) model based identified regulator genes (RLRGs) related HBV infection through WGCNA analysis. We also explored microenvironment intercellular communication score. Additionally, prognostic risk fatty metabolism-associated RLRGs was constructed using TCGA database, association immune infiltration, mutations, drug sensitivity analyzed. vitro vivo experiments were performed investigate RLRG CLTC metabolism progression. Using scRNA-seq HCC, established infection. Moreover, more suppressive stronger displayed cells high scores. The cell trajectory cellular analysis exhibited significant between RLRGs. consisting 8 which effectively evaluated value, status microenvironment, gene chemotherapeutic for patients. Notably, validation suggested that could regulate formation facilitate HCC. Collectively, proposes value. CLTC, regulator, emerges as promising biomarker target, offering new insights into treatment strategies

Language: Английский

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STING in Cancer Immunoediting: Modeling Tumor-Immune Dynamics Throughout Cancer Development

Cancer Letters, Journal Year: 2025, Volume and Issue: 612, P. 217410 - 217410

Published: Jan. 16, 2025

Language: Английский

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