Cold and hot tumors: from molecular mechanisms to targeted therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Язык: Английский

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Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 9, 2025

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and crucial determinant progression. Research indicates that various metabolic regulators form network in TME interact with immune cells, coordinating response. dysregulation creates an immunosuppressive TME, impairing antitumor In this review, we discuss how affect cell crosstalk TME. We also summarize recent clinical trials involving challenges metabolism-based therapies translation. word, our review distills key regulatory factors their mechanisms action from complex metabolism, identified as regulators. These provide theoretical basis research direction for development new strategies targets therapy based on reprogramming. Refining Depicting between stromal cells during Emphasizing unresolved translation advantages personalized treatment. Providing support therapies.

Язык: Английский

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Functionalized biomimetic nanoparticles loaded with salvianolic acid B for synergistic targeted triple-negative breast cancer treatment

Materials Today Bio, Год журнала: 2025, Номер 30, С. 101441 - 101441

Опубликована: Янв. 1, 2025

The therapeutic effect of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) is unsatisfactory. "cold" microenvironment caused by tumor-associated fibroblasts (TAFs) has an adverse on the antitumor response. Therefore, this study, mixed cell membrane-coated porous magnetic nanoparticles (PMNPs) were constructed to deliver salvianolic acid B (SAB) induce response, facilitating transition from a "hot" tumor and ultimately enhancing efficacy inhibitors. PMNP-SAB, which based coating red blood membrane TAF (named PMNP-SAB@RTM), can simultaneously achieve dual effects "immune escape" "homologous targeting". Under influence external field (MF), SAB be targeted concentrated at site. released tumors effectively inhibit production extracellular matrix (ECM) TAFs, promote T-cell infiltration, responses. Ultimately, combination PMNP-SAB@RTM BMS-1 (PD-1/PD-L1 inhibitor 1) inhibited growth. Finally, study presents precise effective new strategy for TNBC immunotherapy basis differentiation microenvironments.

Язык: Английский

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Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy

Nano Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Recent advancements in cancer therapy have highlighted the dual role of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) both cell cycle regulation and immune activation. However, applying CDK4/6i to immunologically unfavorable tumors is challenging due complex tumor microenvironment (TME), characterized by inadequate T recruitment exclusion mechanisms that hinder an effective antitumor immunity. In this work, we iteratively designed prodrug liposomal nanocarriers integrate multiple functions: inhibition through encapsulation CDK4/6i, activation via concurrent delivery oral gavage-inducing chemotherapy agent, overcoming incorporation a cholesterol prodrug. This iterative nanocarrier design effectively improves pharmacokinetic profile overcomes immunosuppressive TME, achieves superior efficacy, synergizes with checkpoint provide lasting effects various colon animal models.

Язык: Английский

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RNA modifications in cancer

MedComm, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Язык: Английский

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The possible anti-tumor effects of regulatory T cells plasticity / IL-35 in the tumor microenvironment of the major three cancer types

Cytokine, Год журнала: 2024, Номер 186, С. 156834 - 156834

Опубликована: Дек. 17, 2024

Язык: Английский

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Emerging Mechanisms and Biomarkers Associated with T-Cells and B-Cells in Autoimmune Disorders

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Фев. 11, 2025

Язык: Английский

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The role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 12, 2025

Background Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an E3 ubiquitin ligase and scaffolding protein that contribute to the progression of various malignant tumors. However, role TRAF2 expression in epigenetic, cancer prognosis, immune responses tumor microenvironment unclear. Methods We used The Human Protein Atlas (HPA) database, TIMER 2.0 TCGA database evaluate human normal tissues. Correlation with mutations epigenetic tumors was evaluated using cBioPortal platform GSCA database. To assess prognostic value TRAF2, we performed Kaplan-Meier plots Cox regression analysis. LinkedOmics for PANTHER Pathways enrichment relationship between checkpoint genes, as well cell infiltration, examined R language. Single-cell sequencing data multiple immunofluorescence staining were observe co-expression on hepatocellular carcinoma cells cells. Furthermore, siRNA-mediated knockdown, explored potential liver biology. Results Our findings indicate frequently mutated significantly overexpressed types cancers, this overexpression linked a poor prognosis. alterations significant across cancers. levels genes tumor-infiltrating cells, suggesting its involvement microenvironment. Of note, analysis revealed correlation T activation, single-cell indicated In vivo results demonstrated closely lymphocytes carcinoma. our vitro experimental studies confirmed loss function inhibits behavior HepG2 Conclusion represents biomarker therapeutic target immunotherapy, particularly patients

Язык: Английский

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Multi-functional lipid nanoformulations for enhancing the efficacy of mRNA tumor vaccines by reversing tumor immunosuppressive microenvironment

Nano Today, Год журнала: 2025, Номер 63, С. 102757 - 102757

Опубликована: Апрель 14, 2025

Язык: Английский

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PRMT5 Inhibitor Synergizes with Chemotherapy to Induce Resembling Mismatch Repair Deficiency and Enhance Anti‐TIGIT Therapy in Microsatellite‐Stable Colorectal Cancer

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Abstract Microsatellite stable (MSS) colorectal cancer (CRC) is considered an “immune‐cold” tumor, accounting for ≈85% of all CRC cases. The overall response rate to chemotherapy combined with immune checkpoint inhibitors in MSS typically less than 10%. specific mechanism that enhances sensitivity and mediated immunogenicity renders more responsive immunotherapy remains elusive. Experiments this study identify a DNA damage repair‐related epigenetic gene, protein arginine methyltransferase 5 (PRMT5), whose inhibition Irinotecan (CPT‐11) synergistically induces postmeiotic segregation increased 2 (PMS2)‐deficient‐like state, leading the release cytosolic double‐stranded DNA. This activates cyclic GMP‐AMP synthase (cGAS)‐stimulator IFN gene (STING) signaling pathway, thereby enhancing anti‐tumor through dendritic cell‐T cell‐dependent functions. Importantly, combining drug GSK3326595 CPT‐11 significantly upregulates receptor tyrosine‐based inhibitory motif (TIGIT) level on CD8+ T cells subsequently demonstrates impressive efficacy vivo when additional anti‐TIGIT included. Collectively, reveals crucial role PRMT5 blockade inducing mismatch repair deficiency‐like state provides novel triple‐drug combination therapy strategy as potential treatment patients CRC.

Язык: Английский

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