Furthermore, caulerpin or a p53 inhibitor (pifithrin-α) modulated CTX-induced M1 polarization in macrophages, thereby delaying GC senescence. These findings demonstrated that caulerpin contributes to alleviating CTX-induced ovarian toxicity by modulating M1 macrophage polarization through the p53/NF-κB signaling pathway, which promotes the senescence of GCs by inducing ROS production.Thus, caulerpin may be a potential therapeutic strategy for breast cancer patients.

Through in vivo and in vitro experiments, BRD4 upregulation was found to already occur during GPL, affecting macrophage polarization and epithelial cell cancerization. This finding provides an experimental basis for strategies targeting BRD4 inhibition at this critical stage.

We show that stromal cell-mediated suppression of macrophage phagocytosis is mediated in part through PD-1 signaling. These data suggest that re-stratification of CRC by CMS may reveal patient subsets with microsatellite stable tumors, particularly CMS4-like tumors, that may respond to immunotherapies.

P=N/A, N=10, Recruiting, Affiliated Hospital of Nantong University

In addition, we highlight the molecular regulatory mechanisms that affect immune system function by exciting or suppressing PrCR. Finally, we review the research advances in tumour therapy by activating PrCR and discuss the challenges and potential solutions to smooth the way for tumour treatment strategies that target PrCR.

P1/2, N=35, Completed, Lawrence Feldman, MD | Active, not recruiting --> Completed

A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction...Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

NNMT+ CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.

Irisin alleviated inflammatory pain by modulating local tissue inflammation and peripheral and central neuroinflammation and reducing glial cell activation and M2 macrophage polarization by modulating the TLR4-MyD88-IRF5 signaling pathway. Accordingly, irisin is a promising candidate for treating inflammatory pain in various diseases.

Furthermore, Dual blockade of Pim1 and PD-1 collaboratively suppressed tumor growth, repolarized macrophages, and boosted the efficacy of anti-PD-1 antibody. Collectively, our findings elucidate the pivotal role of PIM1 in orchestrating TAMs within the TME of NSCLC and highlight the potential of PIM1 inhibition as a strategy for enhancing the efficacy of cancer immunotherapy.

MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.

NIPP is a safe and robust oxidative stress inducer and showed potential in TAM regulation by promoting M1 macrophage polarization.

Analysis of single cell RNA sequencing of macrophages isolated from these tumors reveals that depletion of LYVE-1+ macrophages in tumors drives a shift in the majority of the remaining macrophages towards a pro-inflammatory phenotype, as well as an increase in CD8+ T cell infiltration. Together, these findings indicate that LYVE-1+ macrophages represent a tumor-promoting anti-inflammatory subset of macrophages that contributes to hyaluronan remodeling in the tumor microenvironment.

In vivo animal studies demonstrated that targeting NAT10 could enhance the therapeutic effect of PD-1 on ESCC by mediating macrophage reprogramming. Our findings offer novel insights into improving ESCC treatment through NAT10 targeting.

SA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.

ALKBH5 participated in regulating macrophage M2 polarization in ovarian cancer immune microenvironment.

In addition, these nanosponges exhibited undetectable biotoxicity, making them suitable for clinical applications. In summary, we provide a promising and facile strategy for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.

Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.

P1, N=5, Terminated, HiberCell, Inc. | N=45 --> 5 | Trial completion date: Apr 2027 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Mar 2024; sponsor decision

Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer.

RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients.

It also reduced the expression of angiogenesis and cell proliferation markers in tumour tissues, decreased the quantity of M2 macrophages and their associated markers and pathway proteins. In conclusion, CuB impedes osteosarcoma progression by inhibiting M2 macrophage differentiation via the PI3K/AKT pathway, presenting the potential for therapeutic advancements in osteosarcoma treatment.

Our findings indicate that the antigens from H. polygyrus markedly alter macrophage behavior and increase the proliferation of breast cancer cells in a laboratory setting. This study contributes to a deeper understanding of the complex interactions between parasitic infections and cancer development, highlighting the need for further research in this area to develop potential new strategies for cancer treatment.

P1, N=6, Recruiting, Carisma Therapeutics Inc

This study demonstrated that WL modulated macrophage polarization against liver fibrosis mainly by inhibiting the activation of the TLR4-NF-κB signaling pathway.

Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

These findings suggest that PIMP may positively influence inflammatory responses and alleviate colitis. This study is the first to demonstrate the potential of PIMP as a functional food for the prevention and treatment of colitis.

Blocking protein trafficking in neurons reduced the effect of CM, suggesting that the hyperexcitable state resulted from changes in Na channel trafficking. These results suggest that DRG macrophages, primed by peripheral nerve injury, contribute to neuron-glia crosstalk, Na channel dysregulation and neuronal hyperexcitability implicated in the development of neuropathic pain.

siMerTK delivery combined with PD-1 blockade further produces enhanced antimetastatic efficacy with reactivated intratumoral immune milieu. Collectively, LNP-based siMerTK delivery combined with immune checkpoint therapy may present a feasible modality for metastatic colorectal cancer therapy.

BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19. Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.

Our study demonstrates that exosomal miR-138-5p from irradiated tumor cells can modulate macrophage polarization by targeting SHP-2. And SHP-2 negatively regulates glycolysis and polarize macrophage to an M2 phenotype by SHP-2/PKM2(Tyr105) (Ser37)/β-catenin/LDHA/Glut-1 axis.

Thus, the SHP099 (a SHP-2 inhibitor) can uptake and utilization of glucose by SHP-2/PKM2(Tyr105) (Ser37)/ß-catenin/LDHA/Glut-1 axis, suggesting that SHP099 plays positive roles on glycolysis and M1-polarized... Our study demonstrates that exosomal miR-138-5p from irradiated tumor cells can modulate macrophage polarization by targeting SHP-2. And SHP-2 negatively regulates glycolysis and polarize macrophage to an M2 phenotype by SHP-2/PKM2(Tyr105) (Ser37)/ß-catenin/LDHA/Glut-1 axis.

P1, N=45, Recruiting, HiberCell, Inc. | N=30 --> 45 | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Mar 2025 --> Nov 2025

Overexpressing MEG3 suppressed M2 polarization-induced HCC cell metastasis and angiogenesis by upregulating DAB2 and inhibited in vivo tumor growth. LncRNA MEG3 curbs HCC development by repressing M2 macrophage polarization via miR-145-5p/DAB2 axis.

P2, N=26, Completed, HiberCell, Inc. | Active, not recruiting --> Completed | N=50 --> 26 | Trial completion date: Jan 2027 --> Apr 2023 | Trial primary completion date: Jan 2025 --> Mar 2023

miR-210 can promote autophagy of M2 macrophages via PI3K/AKT/mTOR signaling pathway. M2 macrophage-derived miR-210 promotes the malignant progression of HCC via autophagy, suggesting that macrophage autophagy may serve as a new therapeutic target for HCC, and targeting miR-210 may reset the effect of M2 macrophages on HCC.

OSMR deficiency aggravated pressure overload-induced cardiac hypertrophy by modulating macrophages and OSM/LIFR/STAT3 signalling, which provided evidence that OSMR might be an attractive target for treating pathological cardiac hypertrophy and heart failure.

5 US sites will participate. Clinical trial information: NCT04834778.

Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC.

Mechanistically, we found that redox effector factor-1 (Ref-1) secreted by breast cancer cells activated hypoxia inducible factor-1α (HIF-1α) expression and inhibited reactive oxygen species (ROS) production in Schwann cells, ultimately inducing CXCL2 expression in Schwann cells. In brief, the present study expands new insights into cancer pain mechanisms from promising animal models to provide new strategies for the control of cancer pain.