Editorial: Hiding Features in Myeloid Cells: Metabolism Preference in Different Disease Models

Jie Shen ¹ DuoYao Cao ^2*

• ¹ Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
• ² Cedars Sinai Medical Center, Los Angeles, United States

Cancer Therapy and Myeloid Metabolism: Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) rewire their metabolic programs to favor tumor growth, immune evasion, and therapy resistance. Enhanced fatty acid oxidation (FAO), cholesterol metabolism, and glycolysis in these cells create a tumor-supportive microenvironment. Clinically, metabolic reprogramming can explain the limited efficacy of current immunotherapies in tumors with high TAM or MDSC infiltration. Drugs targeting lipid metabolism, such as inhibitors of CD36 or fatty acid transport proteins, have shown potential in preclinical models by reducing TAM-driven immune suppression and boosting T-cell-mediated anti-tumor responses. Neurodegenerative Diseases : Metabolic dysfunction in microglia, driven by lipid overload and sTREM2 dysregulation, has been implicated in diseases like Alzheimer's. Elevated sTREM2 levels in cerebrospinal fluid (CSF) correlate with microglial activation during the early stages of neurodegeneration, suggesting its potential as both a biomarker and a therapeutic target. Strategies to modulate microglial metabolism-such as reducing lipid accumulation or enhancing phagocytic efficiency-could slow disease progression. Clinical trials investigating sTREM2 agonists or lipid metabolism modulators may hold promise for altering the trajectory of Alzheimer's and other neurodegenerative conditions (DOI: 10.3389/fnagi.2024.1420731).Hematopoietic Cell Metabolism in Regenerative Medicine: Hematopoietic stem cells (HSCs) exhibit distinct metabolic profiles that support their self-renewal and differentiation capacities. High oxidative phosphorylation and fatty acid oxidation activity in HSCs underlie their resilience and therapeutic potential in bone marrow transplantation and regenerative medicine. Clinically, modulating these metabolic pathways could improve the engraftment and functionality of HSCs in treating hematological disorders (DOI: 10.3389/fimmu.2024.1425585).In atherosclerosis, lipid-laden macrophages contribute to plaque instability and chronic inflammation. Targeting metabolic pathways, such as inhibiting CD36-mediated lipid uptake, has shown potential in stabilizing plaques and reducing macrophage-driven inflammation. Emerging therapeutic approaches aim to reprogram these foam cells toward a less inflammatory phenotype, thereby improving cardiovascular outcomes and reducing the risk of acute events like myocardial infarction (DOI: 10.3389/fimmu.2024.1468957).Immunometabolism in Chronic Inflammation and Autoimmunity: Aberrant heme metabolism in myeloid cells, driven by dysregulated heme oxygenase-1 (HO-1) activity, exacerbates inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease. Pharmacological modulation of HO-1 activity could restore immune balance by reducing oxidative stress and inflammation. Clinically, HO-1 inducers or inhibitors may emerge as adjunct therapies for managing autoimmunity and chronic inflammatory disorders (DOI: 10.3389/fimmu.2024.1433113).The integration of metabolic reprogramming strategies with existing therapies offers opportunities for personalized medicine. For instance: 1) Combining lipid metabolism inhibitors with immunotherapy could enhance the efficacy of checkpoint inhibitors in resistant tumors. 2)Using sTREM2-targeted therapies in conjunction with amyloid-beta clearance strategies might amplify therapeutic effects in Alzheimer's patients. 3) Modulating metabolic pathways in myeloid cells during hematopoietic cell transplantation could improve patient outcomes in leukemia and lymphoma Metabolic interventions represent a promising frontier in precision medicine. By targeting specific metabolic vulnerabilities in myeloid cells, we can not only reshape the immune landscape but also enhance the efficacy of current therapies across multiple diseases. Moving forward, clinical trials should focus on validating these metabolic strategies in diverse patient populations, with particular attention to biomarkers like sTREM2 and CD36 for patient stratification and treatment monitoring. The transformative potential of these insights lies in their ability to bridge basic research and clinical practice, offering hope for tackling some of the most challenging diseases of our timecancer, neurodegeneration, and metabolic disorders-through the lens of immunometabolism.The author declares that there is no conflict of interest regarding the publication of this article.