M2 Macrophages Research Articles

Oleanolic acid inhibits M2 macrophage polarization and potentiates anti-PD-1 therapy in hepatocellular carcinoma by targeting miR-130b-3p-PTEN-PI3K-Akt signaling and glycolysis.

Oleanolic acid inhibits M2 macrophage polarization and potentiates anti-PD-1 therapy in hepatocellular carcinoma by targeting miR-130b-3p-PTEN-PI3K-Akt signaling and glycolysis.

LKB1 activated by NaB inhibits the IL-4/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization.

LKB1 activated by NaB inhibits the IL-4/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization.

Vitamin D enhances the effect of Soufeng sanjie formula in alleviating joint inflammation in CIA mice through VDR-NOTCH3/DLL4 signaling in macrophages.

Vitamin D enhances the effect of Soufeng sanjie formula in alleviating joint inflammation in CIA mice through VDR-NOTCH3/DLL4 signaling in macrophages.

Invitro and invivo study of concentrated growth factor (CGF) mediating macrophage polarization in bone defect repair.

Invitro and invivo study of concentrated growth factor (CGF) mediating macrophage polarization in bone defect repair.

FOXC1 promotes EMT and colorectal cancer progression by attracting M2 macrophages via the TGF-β/Smad2/3/snail pathway.

FOXC1 promotes EMT and colorectal cancer progression by attracting M2 macrophages via the TGF-β/Smad2/3/snail pathway.

Effect of a systemically administered innate immune modulator on anti-tumor activity against metastatic osteosarcoma.

e23504 Background: Osteosarcoma (OSa) is the most common malignant bone tumor with limited treatment options and poor outcomes in advanced metastatic cases. In recent decades, significant progress in OSa treatment has been limited, highlighting the urgent need for novel therapeutic approaches. Current immunotherapies, like immune checkpoint inhibitors, have shown insufficient clinical efficacy but recently, systemic activation of innate immune system with Toll-like receptor 4 (TLR4) immunostimulants has shown great promise. Unfortunately, all current TLR4 agonists are restricted to local administration due to toxicity issues limiting their capacity to address metastases and disseminated tumors. Methods: In this study, we explored the antitumor effects of an innovative chemically detoxified TLR4 agonist formulated in liposomes (HEPHA-440) in two syngeneic mouse and rat models of metastatic OSa (LM8 and OsA). HEPHA-440 was shown to have an optimized safety and solubility profile for systemic administration. We evaluated the impact of HEPHA-440 on tumor growth, lung metastases, and immune cell infiltration in wild-type and TLR4-mutant mice and performed selective immunodepletions and transcriptomic analysis in tumors. Results: HEPHA-440 showed potent antitumor effects against both localized OSa tumors, associated with increased tumor necrosis and promotion of CD8+ T cell and M1 macrophage infiltration. HEPHA-440 also significantly reduced the incidence of pulmonary metastases with up to 40% of complete regression. This was associated with a reshape of the tumor microenvironments with infiltration of CD8 + T cells and M1 macrophages in primary tumors, and CD8 + T cells infiltration with a shift of macrophages towards an M1 phenotype in lung metastases. In vitro studies confirmed that HEPHA-440 can reverse the polarization of M2 macrophages toward an M1 phenotype. The antitumor effects of HEPHA-440 were dependent on TLR4 and CD8+ T cells, and treatment increased the expression of immune checkpoint proteins (PD1, PD-L1, LAG-3 and OX40L) in OSa tumors. Furthermore, analysis of a publicly available dataset for patients with OSa revealed that higher infiltration of CD8+ T cells and M1 macrophages was correlated with better overall survival and progression-free survival. Conclusions: These findings demonstrated for the first time that a detoxified TLR4 immunostimulant can address metastatic osteosarcoma, thanks to systemic administration and capacity to reprogram tumor microenvironments through the recruitment of CD8 T-cells and M1 macrophages, and the repolarization of M2 tumor associated macrophages toward an M1 phenotype. Our data also suggest that HEPHA-440 could make OSa tumors finally responsive to Immune Checkpoint Inhibitor (ICI) treatments. This warrants further development toward clinical evaluation in cancer patients.

LTK deficiency induces macrophage M2 polarization and ameliorates Sjogren's syndrome by reducing chemokine CXCL13.

LTK deficiency induces macrophage M2 polarization and ameliorates Sjogren's syndrome by reducing chemokine CXCL13.

Macrophage membrane-coated polydopamine nanomedicine for treating acute lung injury through modulation of neutrophil extracellular traps and M2 macrophage polarization.

Macrophage membrane-coated polydopamine nanomedicine for treating acute lung injury through modulation of neutrophil extracellular traps and M2 macrophage polarization.

MiR-146a is critical for orchestrating Mycobacterium fortuitum survival through anti-inflammatory and M2 macrophage responses in fish.

miR-146a is critical for orchestrating Mycobacterium fortuitum survival through anti-inflammatory and M2 macrophage responses in fish.

Human amniotic mesenchymal stem cells improve patency and regeneration of electrospun biodegradable vascular grafts via anti-thrombogenicity and M2 macrophage polarization.

Human amniotic mesenchymal stem cells improve patency and regeneration of electrospun biodegradable vascular grafts via anti-thrombogenicity and M2 macrophage polarization.

RGD peptide/dextran sulfate-based nanocarriers loaded with triptolide for double-targeted apoptosis of both tumor cells and M2-like TAMs in pancreatic cancer therapy.

RGD peptide/dextran sulfate-based nanocarriers loaded with triptolide for double-targeted apoptosis of both tumor cells and M2-like TAMs in pancreatic cancer therapy.

Combined metabolomics and network pharmacology to elucidate the mechanisms of Huiyang Shengji decoction in treating diabetic skin ulcer mice.

Combined metabolomics and network pharmacology to elucidate the mechanisms of Huiyang Shengji decoction in treating diabetic skin ulcer mice.

M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis.

M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis.

Luteolin inhibits inflammation and M1 macrophage polarization in the treatment of Pseudomonas aeruginosa-induced acute pneumonia through suppressing EGFR/PI3K/AKT/NF-κB and EGFR/ERK/AP-1 signaling pathways.

Luteolin inhibits inflammation and M1 macrophage polarization in the treatment of Pseudomonas aeruginosa-induced acute pneumonia through suppressing EGFR/PI3K/AKT/NF-κB and EGFR/ERK/AP-1 signaling pathways.

The crosstalk between lung adenocarcinoma cells and M2 macrophages promotes cancer cell development via the SFRS1/miR-708-5p/PD-L1 axis.

The crosstalk between lung adenocarcinoma cells and M2 macrophages promotes cancer cell development via the SFRS1/miR-708-5p/PD-L1 axis.

MiRNA let-7-5p present in the extracellular vesicles of Trichinella spiralis newborn larvae inhibits the function of M1-type RAW264.7 macrophages by targeting C/EBPδ

Abstract Background Trichinella spiralis, in its newborn larva (NBL) stage, invades the host bloodstream and disseminates throughout the body. Concurrently, M1 macrophages undergo transformation into M2 macrophages. In our previous studies, we demonstrated that extracellular vesicles secreted by NBL (NBL-EVs) significantly express the microRNA (miRNA) cel-let-7-5p. In this study, we investigated the immunomodulatory effects and mechanisms of action of EVs derived from T. spiralis NBL and the influence of their key miRNA, cel-let-7-5p, on M1 macrophages. Methods This study investigates the impact of T. spiralis NBL-EVs and cel-let-7-5p on RAW264.7 macrophages through in vitro co-culture, followed by a dual luciferase assay to confirm C/EBPδ as the target of cel-let-7-5p. M1-polarized RAW264.7 cells were subsequently transfected with various agents, including NBL-EVs, cel-let-7-5p mimic, C/EBPδ small interfering RNA (siRNA), and so forth. The cell functions, surface molecule expression, transcription, and cytokine release were analyzed using flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) to elucidate the regulatory mechanisms of NBL-EVs and cel-let-7-5p on macrophage polarization. Results Results show that cel-let-7-5p transported by T. spiralis NBL-EVs inhibited the functional activity of M1 RAW264.7 macrophages by targeting C/EBPδ. This inhibition was validated by reduced CD86 and increased CD206 expression, along with decreased nitric oxide (NO) synthesis and downregulation of the M1 marker genes interleukin-12 (IL-12) and inducible nitric oxide synthase (iNOS). In contrast, the messenger RNA (mRNA) levels of IL-10 and arginase-1 (Arg1), which are M2 characteristic genes, were significantly enhanced. However, the release of M1 pro-inflammatory cytokines, such as IL-6, tumor necrosis factor-alpha (TNF-α), and IL-1β, was decreased proportionally. Notably, introducing a cel-let-7-5p inhibitor effectively reversed the suppressive effect of NBL-EVs on M1 macrophage function and partially mitigated their transition to the M2 phenotype, notably impacting Arg1 gene expression. However, no significant changes were observed in CD206 protein expression or IL-10 mRNA levels. Conclusions The findings of this study reveal that cel-let-7-5p in T. spiralis NBL-EVs can inhibit the function of M1-type RAW264.7 macrophages by targeting C/EBPδ. Graphical Abstract

Dual-targeted microbubbles for atherosclerosis therapy: Inducing M1 macrophage apoptosis by inhibiting telomerase activity.

The progression of atherosclerosis (AS) is closely associated with M1 macrophages. Although the activation of macrophage telomerase during plaque formation has been documented, targeted modulation strategies remain challenging. In this study, we developed a dual-target microbubble-delivery system (Ab-MMB1532) encapsulating BIBR1532, a telomerase inhibitor, for the targeted therapy of AS. This system exhibited remarkable targeting capabilities towards M1 macrophages, with its targeting advantage notably accentuated under high shear forces. Mechanistically, Ab-MMB1532 inhibited telomerase activity by downregulating telomerase reverse transcriptase (TERT) expression, subsequently inducing caspase-3-mediated apoptosis. Integrated multi-omics profiling revealed that the inhibition of the NF-κB pathway served as the central regulatory hub. In vivo studies further confirmed that Ab-MMB1532 effectively targets and accumulates within AS lesions, promoting M1 macrophage apoptosis through the inhibition of the TERT/NF-κB signaling axis, and significantly reducing plaque burden (25.4% reduction vs. controls, p<0.001). In summary, our findings suggest a novel approach for telomerase-targeted therapy in AS.

OGT-regulated O-GlcNAcylation promotes the malignancy of colorectal cancer by activating STAT2 to induce macrophage M2: OGT protein macromolecule action.

OGT-regulated O-GlcNAcylation promotes the malignancy of colorectal cancer by activating STAT2 to induce macrophage M2: OGT protein macromolecule action.

SNHG16 suppression enhances M2 macrophage polarization and inhibits VSMC migration in atherosclerosis.

SNHG16 suppression enhances M2 macrophage polarization and inhibits VSMC migration in atherosclerosis.

Lipid metabolic gene expression and association with decreased overall survival and immunogenicity in KRAS-STK11 NSCLC.

8534 Background: Approximately 30% of patients (pts) with non-small cell lung cancer (NSCLC) have alterations (alt) in KRAS . How co-alt such as STK11 affect the tumor microenvironment and survival requires further characterization. Recently, our group found that lower expression of lipid metabolic genes in KRAS G12C co-alt tumors was associated with worse overall survival (OS). Here, we seek to confirm these findings utilizing a large real-world (rw) patient de-identified database. Methods: Approximately 2,187 pts (61%, stage IV) with KRAS G12C alt NSCLC who underwent sequencing via the Tempus xT/xR assay with co-alt in TP53 (44%) , STK11 (17%), or LRP1B (4%) were selected. The groups are mutually exclusive. Single-sample GSEA (ssGSEA) based on 775 lipid metabolic genes (LMG) was used to calculate enrichment scores (LMG ES) for each pt. Pts were dichotomized into low vs. high groups based on their median LMG ES. Immune cell infiltration predicted from gene expression patterns, TMB, and PD-L1 from IHC was evaluated. Risk-set adjusted rwOS was calculated from sample collection date to death from any cause. Hazard ratios (HR) were calculated using Cox proportional hazards model, and p-values were calculated using the Wald test. Results: Among pts with KRAS G12C alt, the median age was 68, 58% were female, and 84% were White. Pts with KRAS G12C/ STK11 alt had the lowest TMB, neoantigen burden, and PDL-1 positivity compared to other cohorts (p&lt;0.001 for all). Importantly, the proportion of total immune cells, M1, M2, NK cells, CD8 T cells and regulatory T cells was lowest in tumors with KRAS G12C/ STK11 alt (p&lt;0.001 for all). To determine if lipid genes were associated with immunogenic changes, LMG ES was compared to immune infiltration. The ES was associated with immune cell infiltration percentages for M1 macrophages (OR 1.11 (1.03-1.21) p=0.012), M2 macrophages (OR 1.27 (1.15-1.40) p&lt;0.001) and neutrophils (OR 1.12 (1.04-1.22) p=0.005), with a trend towards significant association with CD4 T cells (OR 1.08 (1.00-1.17) p=0.062). Pts with KRAS G12C/STK11 alt and low LMG ES had decreased median rwOS ( 5.4 vs 18.2 months, p=0.0002 ) compared to pts with a high ES. Multivariate analysis demonstrated that lower LMG ES correlated with reduced rwOS (HR = 1.75 (1.22-2.51, p = 0.002) compared to pts with high ES. Individual gene analysis showed that low LPL (HR = 1.85 (1.147-2.97) p=0.012), LDLRAD4 (HR = 1.72 (1.082-2.72) p = 0.022) and LDLR (HR = 1.58 (1.009-2.46) p=0.045) expression was associated with poorer rwOS. Conclusions: Low lipid gene expression in KRAS - STK11 NSCLC was associated with decreased OS. Lipid gene expression and tumor immune cell infiltration were associated, suggesting that lipid metabolism may regulate tumor immunogenicity. These data suggest that lipid metabolic genes should be further explored as potential therapeutic targets for pts with NSCLC and KRAS - STK11 alt.