The role of tumor-associated macrophages in tumor immune evasion

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

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Reprogramming exosomes for immunity-remodeled photodynamic therapy against non-small cell lung cancer

Bioactive Materials, Journal Year: 2024, Volume and Issue: 39, P. 206 - 223

Published: May 21, 2024

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, minimal adverse effects. The combination of photodynamic therapy (PDT) immunotherapy gradually become a promising approach high-grade malignant NSCLC. Nevertheless, owing the absence precise drug delivery techniques as well hypoxic immunosuppressive characteristics tumor microenvironment (TME), efficacy less than ideal. In study, we construct novel nanoplatform indocyanine green (ICG), photosensitizer, loads into hollow manganese dioxide (MnO

Language: Английский

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METTL14 regulates microglia/macrophage polarization and NLRP3 inflammasome activation after ischemic stroke by the KAT3B-STING axis

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 185, P. 106253 - 106253

Published: Aug. 2, 2023

N6-methyladenosine (m6A) plays a crucial role in ischemic stroke, whereas the of methyltransferase-like 14 (METTL14) stroke remains unknown. A model middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cells were used to simulate vivo vitro. We found that METTL14 level was upregulated microglia/macrophage after MCAO OGD/R. enhanced expression KAT3B by promoting m6A modification mRNA. STING has been identified as target for increased enhancing H3K27ac promoter. promoted M1 polarization NLRP3 inflammasome/pyroptosis axis KAT3B-STING signaling depletion relieved brain injury inhibiting M1-like rats. These findings indicate relieves MCAO-induced injury, probably via switching from towards M2 restraining microglia/macrophage.

Language: Английский

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Hypoxia-induced ALKBH5 aggravates synovial aggression and inflammation in rheumatoid arthritis by regulating the m6A modification of CH25H

Clinical Immunology, Journal Year: 2024, Volume and Issue: 261, P. 109929 - 109929

Published: Feb. 6, 2024

Language: Английский

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METTL3-mediated N6-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4

Oncogene, Journal Year: 2024, Volume and Issue: 43(30), P. 2338 - 2354

Published: June 15, 2024

Abstract N 6 -methyladenosine (m A) is the predominant post-transcriptional RNA modification in eukaryotes and plays a pivotal regulatory role various aspects of fate determination, such as mRNA stability, alternative splicing, translation. Dysregulation critical m A methyltransferase METTL3 implicated tumorigenesis development. Here, this work showed that upregulated gastric cancer tissues associated with poor prognosis. methylates A2318 site within coding sequence (CDS) region STAT5A. IGF2BP2 recognizes binds METTL3-mediated STAT5A through its GXXG motif KH3 KH4 domains, leading to increased stability mRNA. In addition, both are positively correlated human tissue samples. Helicobacter pylori infection expression level cells, thereby upregulation Functional studies indicated overexpression markedly enhances proliferation migration GC whereas knockdown has inhibitory effects. Further nude mouse experiments effectively inhibits growth metastasis vivo. Moreover, transcription factor, represses KLF4 by binding promoter region. The can counteract oncogenic impact Overall, study highlights crucial provides potential therapeutic targets for cancer.

Language: Английский

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RNA modifications in cancer

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 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.

Language: Английский

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WTAP suppresses STAT3 via m6A methylation to regulate autophagy and inflammation in central nervous system injury

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106811 - 106811

Published: Jan. 1, 2025

Language: Английский

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ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: June 14, 2024

Abstract Background Understanding the mechanisms that mediate interaction between tumor and immune cells may provide therapeutic benefit to patients with cancer. The N6-methyladenosine (m6A) demethylase, ALKBH5 (alkB homolog 5), is overexpressed in non-small cell lung However, its role microenvironment unknown. Methods Datasets tissue samples were used determine relationship expression immunotherapy efficacy. Bioinformatic analysis, colorimetric assay m6A RNA methylation, dual luciferase reporter assay, RNA/m6A-modified immunoprecipitation, stability sequencing investigate regulatory mechanism of In vitro vivo assays performed contribution development Results was upregulated primary cancer tissues. positively correlated programmed death-ligand 1 macrophage infiltration associated response. JAK2 identified as a target ALKBH5-mediated modification, which activates JAK2/p-STAT3 pathway promote progression. found recruit 1-positive tumor-associated macrophages M2 polarization by inducing secretion CCL2 CXCL10. macrophage-secreted IL-6 showed synergistic effect activate cells. Conclusions promotes progression regulating behavior through CXCL10, respectively. These findings suggest targeting promising strategy enhancing anti-tumor response NSCLC identifying status could facilitate prediction clinical anti-PD-L1 immunotherapy.

Language: Английский

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