Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally DOI Creative Commons
Luna Minute,

Marta Bergón-Gutiérrez,

Pablo Mata-Martínez

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108869 - 108869

Published: Jan. 11, 2024

Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering clinical applications harnessing against infections and cancer, there is growing need for new, simple, easy-to-use inducers. Here, we demonstrate that heat-killed Mycobacterium (HKMtb) induces both in vitro vivo. In human monocytes, this effect truly trained process, HKMtb confers boosted inflammatory responses heterologous challenges, lipopolysaccharide (Toll-like receptor [TLR] 4 ligand) R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced relies on epigenetic mechanisms Syk/HIF-1α-dependent manner. vivo, induced when administered systemically intranasally, latter generating more robust response. Summarizing, our research has demonstrated potential to act mucosal immunotherapy successfully induce responses.

Language: Английский

Macrophages at the interface of the co-evolving cancer ecosystem DOI Creative Commons
Daan J. Kloosterman, Leila Akkari

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1627 - 1651

Published: March 15, 2023

Language: Английский

Citations

190
Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity DOI Open Access

Evros Vassiliou,

Renalison Farias‐Pereira

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12032 - 12032

Published: July 27, 2023

Macrophage polarization is influenced by lipids, which also exert significant control over macrophage functions. Lipids and their metabolites are players in intricate signaling pathways that modulate macrophages’ responses to pathogens, phagocytosis, ferroptosis, inflammation. This review focuses on lipid metabolism functions addresses potential molecular targets for the treatment of macrophage-related diseases. While lipogenesis crucial accumulation phagocytosis M1 macrophages, M2 macrophages likely rely fatty acid β-oxidation utilize acids as primary energy source. Cholesterol metabolism, regulated factors such SREBPs, PPARs, LXRs, associated with cholesterol efflux capacity formation foam cells (M2-like macrophages). Foam cells, atherosclerosis, an increase inflammatory cytokines. Lipolysis uptake markers, CD36, contribute production Enhancing immune system through inhibition lipid-metabolism-related can potentially serve a targeted approach against tumor cells. Cyclooxygenase inhibitors, block conversion arachidonic into various mediators, influence have generated attention cancer research.

Language: Английский

Citations

60
Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets DOI Creative Commons
Zihong Wu, Chong Xiao, Jing Long

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 1, 2024

Colorectal cancer (CRC) is a significant public health concern, and its development associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cells owing their plasticity dynamic nature. The fusion-fission dynamics mitochondria play crucial role in signal transduction functions CRC cells. Enhanced fission promotes reprogramming cells, leading cell proliferation, metastasis, chemoresistance. Excessive also trigger mitochondria-mediated apoptosis. In contrast, excessive fusion leads adenosine triphosphate (ATP) overproduction abnormal tumor whereas moderate protects intestinal epithelial from oxidative stress-induced damage, thus preventing colitis-associated (CAC). Therefore, an imbalance either promote or inhibit progression. This review provides overview mechanism underlying impact on biology. revealed dual identified potential drug targets. Additionally, this study partially explored immune vascular endothelial microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Language: Английский

Citations

23
Trained immunity in chronic inflammatory diseases and cancer DOI
George Hajishengallis, Mihai G. Netea, Triantafyllos Chavakis

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Language: Английский

Citations

4
Nebulized Therapy of Early Orthotopic Lung Cancer by Iron-Based Nanoparticles: Macrophage-Regulated Ferroptosis of Cancer Stem Cells DOI

Qishuai Feng,

Wenming Fang,

Yuedong Guo

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24153 - 24165

Published: Oct. 28, 2023

Cancer stem cells (CSCs) within protumorigenic microlesions are a critical driver in the initiation and progression of early stage lung cancer, where immune provide an immunosuppressive niche to strengthen CSC stemness. As mutual interactions between CSCs increasingly recognized, regulating identify effectively eliminate has recently become one most attractive therapeutic options, especially for abundant tumor-associated macrophages (TAMs). Herein, we developed nebulized nanocatalytic medicine strategy which iron-based nanoparticle-regulated TAMs target niches trigger ferroptosis cancer. Briefly, nanoparticles can accumulate cancer (minimum 122 μm diameter) through dextran-mediated TAM targeting by nebulization administration, as result, nanoparticle-internalized play predominant role iron factory elevating level surrounding destroying redox equilibrium downregulating glucose-6-phosphate metabolite following their lysosomal degradation metabolism. The altered microenvironment results enhanced sensitivity due high expression CD44 receptor mediating endocytosis. In orthotopic mouse model significantly suppressed ferroptosis-induced stemness reduction administration. This work presents modulation communications CSCs, is expected be general approach primary micrometastatic

Language: Английский

Citations

33
Trained immunity: Target for prophylaxis and therapy DOI

Athanasios Ziogas,

Mariolina Bruno, Roy van der Meel

et al.

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(11), P. 1776 - 1791

Published: Nov. 1, 2023

Language: Английский

Citations

29
Metabolic Regulation in the Induction of Trained Immunity DOI Creative Commons
Anaísa V. Ferreira, Jorge Domínguez‐Andrés, Laura M. Merlo Pich

et al.

Seminars in Immunopathology, Journal Year: 2024, Volume and Issue: 46(3-4)

Published: July 25, 2024

Abstract The innate immune system exhibits features of memory, termed trained immunity, which promote faster and more robust responsiveness to heterologous challenges. Innate memory is sustained through epigenetic modifications, affecting gene accessibility, promoting a tailored transcription for an enhanced response. Alterations in the landscape are intertwined with metabolic rewiring. Here, we review pathways that underscore induction maintenance including glycolysis, oxidative phosphorylation, tricarboxylic acid cycle, amino lipid metabolism. intricate interplay these pivotal establishing distinct cellular compartments. We explore particular case resident lung alveolar macrophages. propose leveraging may present therapeutic potential. Specifically, targeting programs cells emerging strategy clinical interventions, either boost responses immunosuppressed conditions or mitigate maladaptive activation hyperinflammatory diseases.

Language: Английский

Citations

10
Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity DOI Creative Commons
Cian J. H. Horneck Johnston, Anna E. Ledwith, Mimmi L. E. Lundahl

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109030 - 109030

Published: Jan. 26, 2024

Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 could impact strategies to improve humans. Using a panel diverse β-glucans, we describe ability specific yeast-derived whole-glucan particle (WGP) reprogram metabolism thereby drive human monocyte-derived macrophages

Language: Английский

Citations

9
Inhalable nanoparticles with enhanced cuproptosis and cGAS–STING activation for synergistic lung metastasis immunotherapy DOI Creative Commons

Chongzheng Yan,

Huaiyou Lv,

Yafei Feng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3697 - 3710

Published: May 3, 2024

Due to the insufficient Cu

Language: Английский

Citations

9
Trained immunity inducers in cancer immunotherapy DOI Creative Commons
Yongjun Sui, Jay A. Berzofsky

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

Published: July 16, 2024

While most of the cancer immunotherapy strategies engage adaptive immunity, especially tumor-associated T cells, small fraction responding patients and types cancers amenable, possibility severe adverse effects limit its usage. More effective general interventions are urgently needed. Recently, a de facto innate immune memory, termed ‘trained immunity’, has become new research focal point, promises to be powerful tool for achieving long-term therapeutic benefits against cancers. Trained immunity-inducing agents such as BCG fungal glucan have been shown able avert suppressive tumor microenvironment (TME), enhance cell responses, eventually lead regression. Here, we review current understating trained immunity induction highlight critical roles emergency granulopoiesis, interferon γ tissue-specific induction. Preclinical clinical studies that exploited inducers summarized, repurposed from other fields proposed. We also outline challenges opportunities in future immunotherapies. envisage more vaccines will combine with therapies.

Language: Английский

Citations

9