Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 14, 2023

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cell signals, TAMs exhibit unparalleled adaptability, aligning with dynamic milieu. Their roles span from promoting growth and angiogenesis modulating metastasis. While substantial research has explored fundamentals of TAMs, comprehending their adaptive behavior, leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, complex orchestration cytokines chemokines determining functions. We highlight complexities TAM-targeted focusing on adaptability potential variability in therapeutic outcomes. Moreover, we discuss synergy integrating TAM-focused strategies established treatments, such as chemotherapy, immunotherapy. Emphasis is laid pioneering methods like reprogramming immunotherapy adoption single-cell technologies precision intervention. synthesis seeks shed light TAMs’ multifaceted cancer, pinpointing prospective pathways transformative enhancing modalities oncology.

Language: Английский

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Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 26, 2023

Lactate, traditionally regarded as a metabolic waste product at the terminal of glycolysis process, has recently been found to have multifaceted functional roles in metabolism and beyond. A reprogramming phenomenon commonly seen tumor cells, known "Warburg effect," sees high levels aerobic result an excessive production lactate. This lactate serves substrate that sustains not only survival cancer cells but also immune cells. However, it inhibits function tumor-associated macrophages (TAMs), group innate ubiquitously present solid tumors, thereby facilitating evasion malignant Characterized by their plasticity, TAMs are generally divided into pro-inflammatory M1 phenotype pro-tumour M2 phenotype. Through process 'education' lactate, tend adopt immunosuppressive collaborate with promote angiogenesis. Additionally, there is growing evidence linking epigenetic modifications, suggesting participation histone modification diverse cellular events within microenvironment (TME). In this review, we delve recent discoveries concerning particular focus on impact TAMs. We aim consolidate molecular mechanisms underlying lactate-induced TAM polarization angiogenesis explore lactate-mediated crosstalk between Finally, touch upon latest progress immunometabolic therapies drug delivery strategies targeting production, offering new perspectives for future therapeutic approaches.

Language: Английский

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Nano‐bio interactions between 2D nanomaterials and mononuclear phagocyte system cells

BMEMat, Journal Year: 2024, Volume and Issue: 2(2)

Published: Jan. 10, 2024

Abstract Two‐dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly the realms of immunotherapy tissue engineering tumor therapy. These applications necessitate a thorough assessment potential influence 2D nanomaterials on immune cells. Notably, mononuclear phagocyte system (MPS) cells, which play pivotal roles both innate adaptive immunity, are essential maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to prevention foreign body invasion elimination dead or senescent Furthermore, including macrophages dendritic serve as vital bridges between responses. Therefore, understanding nano‐bio interactions is imperative. cellular uptake, cytocompatibility, immunological impact invaluable purposeful design nanomaterials. Herein, we provide an overview latest advancements discuss current challenges future prospects employing field nanomedicine.

Language: Английский

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Nanomaterials-Involved Tumor-Associated Macrophages’ Reprogramming for Antitumor Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 7769 - 7795

Published: Feb. 29, 2024

Tumor-associated macrophages (TAMs) play pivotal roles in tumor development. As primary contents of environment (TME), TAMs secrete inflammation-related substances to regulate tumoral occurrence and There are two kinds TAMs: the tumoricidal M1-like protumoral M2-like TAMs. Reprogramming from immunosuppressive M2 immunocompetent M1 phenotype is considered a feasible way improve immunotherapeutic efficiency. Notably, nanomaterials show great potential for biomedical fields due their controllable structures properties. many types that exhibit regulatory activities TAMs' reprogramming. In this review, recent progress nanomaterials-involved reprogramming comprehensively discussed. The various strategies summarized introduced. Additionally, challenges perspectives efficient therapy discussed, aiming provide inspiration regulator design promote development TAMs-mediated immunotherapy.

Language: Английский

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Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(2), P. 388 - 406

Published: Feb. 1, 2024

Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins but have been linked to cancer development and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) influences crucial hallmarks through intricate molecular mechanisms, including proliferation, invasion, angiogenesis, apoptosis, the epithelial-mesenchymal transition (EMT). The current article highlights involvement of MALAT-1 in drug resistance, making it a potential target overcome chemotherapy refractoriness. It discusses impact on immunomodulatory molecules, such as major histocompatibility complex (MHC) PD-L1, leading immune evasion hindering anti-tumor responses. also plays significant role immunology by regulating diverse cell populations. In summary, is versatile regulator, influencing tumorigenesis, chemoresistance, immunotherapy Understanding its precise mechanisms developing targeted therapies, therapeutic strategies targeting show promise improving treatment outcomes. However, further research needed fully uncover biology translate these findings into clinical applications.

Language: Английский

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Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Small, Journal Year: 2024, Volume and Issue: 20(35)

Published: April 23, 2024

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles tumor diagnosis treatment lie their ability to target delivery, minimizing toxicity normal tissues while enhancing therapeutic efficacy. Moreover, responsiveness both endogenous exogenous stimuli opens up new possibilities integrating multiple modalities. This review scrutinizes the burgeoning utility combination with chemotherapy other Commencing elucidation synthesis degradation mechanisms, emphasis placed on these materials (e.g., pH, redox reactions, hypoxia, enzymes) light high-intensity focused ultrasound). this exploration delves into strategies harnessing alone, coupled radiotherapy, photothermal therapy, photodynamic gas immunotherapy, starvation chemodynamic elucidating multimodal synergies. Concluding an assessment advances, challenges, constraints oncology, despite hurdles, future investigations are anticipated augment role cancer therapy. These insights can serve a compass devising more efficacious combined strategies.

Language: Английский

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Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: April 11, 2024

Abstract Extracellular vesicles (EVs) have recently received increasing attention as essential mediators of communication between tumor cells and their microenvironments. Tumor-associated macrophages (TAMs) play a proangiogenic role in various tumors, especially head neck squamous cell carcinoma (HNSCC), angiogenesis is closely related to growth metastasis. This research focused on exploring the mechanisms by which EVs derived from TAMs modulate HNSCC. Our results indicated that infiltration correlated positively with microvascular density Then we collected identified TAMs. In microfluidic chip, significantly enhanced angiogenic potential pHUVECs successfully induced formation perfusable blood vessels. qPCR immunofluorescence analyses revealed transferred miR-21-5p endothelial (ECs). And targeting could effectively inhibit TAM-EVs angiogenesis. Western blot tube assays showed downregulated LATS1 VHL levels but upregulated YAP1 HIF-1α levels, inhibitors both reduce HUVECs. The vivo experiments further proved carried promoted process via YAP1/HIF-1α axis Conclusively, TAM-derived ECs target mRNA , inhibited phosphorylation subsequently YAP1-mediated transcription reduced VHL-mediated ubiquitination, contributing These findings present novel regulatory mechanism angiogenesis, miR-21-5p/YAP1/HIF-1α might be therapeutic for

Language: Английский

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Multi‐Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS‐STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 9, 2024

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore surveillance system for robust activation, vast efforts are devoted to normalizing TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed potent anti-tumor immunity by reversing Mn-LDH synthesized via one-step hydrothermal method. In addition inherent proton neutralization capacity LDH, introduction manganese oxide endows LDH with an additional ability produce oxygen. effectively releases Mn

Language: Английский

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Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), tumor-associated macrophages (TAMs), plays key role tumor progression, immune evasion, therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 immunosuppressive M2 phenotypes, with the latter predominating GC contributing outcomes. Recent advancements focus on targeting TAMs, including inhibiting polarization, reprogramming combining TAM-targeted approaches checkpoint inhibitors. Innovations nanotechnology, metabolic reprogramming, pathways such as interleukin-6 C-C motif ligand 2/C-C chemokine receptor 2 further enhance these strategies. However, challenges remain, spatial functional heterogeneity of within TME need for selective avoid disrupting homeostasis. Ongoing research TAM origins, functions, interactions is crucial developing precise effective therapies. These advances hold promise not only improving outcomes but also addressing other cancers similarly complex microenvironments.

Language: Английский

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Macrophage subsets and their role: co-relation with colony-stimulating factor-1 receptor and clinical relevance

Immunologic Research, Journal Year: 2022, Volume and Issue: 71(2), P. 130 - 152

Published: Oct. 21, 2022

Language: Английский

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