{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:12:32Z","timestamp":1788433952828,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The dysregulation of immune homeostasis and the persistence of chronic, low-grade inflammation represent core pathophysiological drivers governing the onset and progression of metabolic and cardiovascular disorders. Myeloid-derived suppressor cells (MDSCs) comprise a highly heterogeneous population of immature myeloid cells that are rapidly mobilized from the bone marrow in response to biological stressors, such as sustained tissue injury and chronic inflammatory signaling. Historically evaluated within oncology and infectious disease frameworks, accumulating evidence highlights the pivotal, context-dependent roles of MDSCs in cardiometabolic environments. In conditions of obesity and type 2 diabetes (T2D), MDSCs undergo substantial expansion and accumulation within peripheral tissues, including adipose tissue and the liver. Functionally, MDSCs act as dynamic immunoregulators that can either buffer metabolic inflammation, via the secretion of interleukin-10 (IL-10), transforming growth factor-beta (TGF-\u03b2), and nitric oxide (NO) or, conversely, reflect and exacerbate disease progression depending on specific cellular subsets, glycemic control, and tissue localization. Within the vascular system, specific monocytic MDSC subsets demonstrate significant atheroprotective and cardioprotective capabilities by dampening Th1\/Th17-mediated arterial wall inflammation, stabilizing atherosclerotic plaques, and preserving cardiac structural architecture during heart failure. However, phenotypic and functional heterogeneity poses a critical clinical challenge, as certain persistent or altered subsets correlate with heightened cardiovascular risk and adverse cerebrovascular outcomes. This review delivers a comprehensive synthesis of contemporary insights into MDSC biology at the intersection of obesity-associated diabetes and cardiovascular disease, characterizing their dualistic mechanisms, distinguishing preclinical causal mechanisms from human observational data. Moreover, we have established a comprehensive framework to reconcile the conflicting protective versus detrimental effects of MDSCs. And finally, we have also evaluated their potential clinical utility as candidate biomarkers, delineating the safety imperatives essential for translating MDSC-targeted therapeutic interventions into clinical practice.<\/jats:p>","DOI":"10.3390\/ijms27177872","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"7872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myeloid-Derived Suppressor Cells (MDSCs) in Cardiovascular Risk of Obesity-Associated Diabetes"],"prefix":"10.3390","volume":"27","author":[{"given":"Roc\u00edo","family":"Flores-Campos","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, School of Medicine, University of Seville, 41009 Seville, Spain"},{"name":"Laboratory Medicine Service, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain"},{"name":"Institute of Biomedicine of Seville, Virgen Macarena\/Virgen Rocio University Hospital, CSIC, University of Seville, 41004 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0582-3386","authenticated-orcid":false,"given":"Lourdes","family":"Hontecillas-Prieto","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, School of Medicine, University of Seville, 41009 Seville, Spain"},{"name":"Laboratory Medicine Service, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-2747","authenticated-orcid":false,"given":"Daniel J.","family":"Garc\u00eda-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, School of Medicine, University of Seville, 41009 Seville, Spain"},{"name":"Institute of Biomedicine of Seville, Virgen Macarena\/Virgen Rocio University Hospital, CSIC, University of Seville, 41004 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-8814","authenticated-orcid":false,"given":"Antonio","family":"Fern\u00e1ndez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Immunology Group of the Spanish Society of Laboratory Medicine (SEMEDLAB), 28010 Madrid, Spain"},{"name":"Servicio Andaluz de Salud, UGC Laboratorios, Hospital Universitario San Agust\u00edn, 23700 Linares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iker","family":"Egusquiza-Lasuen","sequence":"additional","affiliation":[{"name":"Immunology Group of the Spanish Society of Laboratory Medicine (SEMEDLAB), 28010 Madrid, Spain"},{"name":"Osakidetza Basque Health Service, Department of Laboratory, Araba University Hospital, 01009 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5528-1143","authenticated-orcid":false,"given":"Antonio","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Cardiovascular Risk Group of the Spanish Society of Dibetes (SED), 28002 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-4719","authenticated-orcid":false,"given":"Josep","family":"Ribalta","sequence":"additional","affiliation":[{"name":"Cardiovascular Risk Group of the Spanish Society of Dibetes (SED), 28002 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Departament de Medicina i Cirurgia, Unitat de Recerca en L\u00edpids i Arteriosclerosi (URLA), Universitat Rovira i Virgili, 43204 Reus, Spain"},{"name":"Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pedro-Botet","sequence":"additional","affiliation":[{"name":"Cardiovascular Risk Group of the Spanish Society of Dibetes (SED), 28002 Madrid, Spain"},{"name":"Hospital del Mar, Unidad de L\u00edpidos y Riesgo Vascular, 08003 Barcelona, Spain"},{"name":"Departamento de Medicina, Universidad Aut\u00f3noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-8680","authenticated-orcid":false,"given":"V\u00edctor","family":"S\u00e1nchez-Margalet","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, School of Medicine, University of Seville, 41009 Seville, Spain"},{"name":"Laboratory Medicine Service, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain"},{"name":"Immunology Group of the Spanish Society of Laboratory Medicine (SEMEDLAB), 28010 Madrid, Spain"},{"name":"Cardiovascular Risk Group of the Spanish Society of Dibetes (SED), 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Immunology Group of the Spanish Society of Laboratory Medicine (SEMEDLAB)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Cardiovascular Disease Group of the Spanish Diabetes Society (SED)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.32553\/jbpr.v14i2.1258","article-title":"The Role of the Immune System in Maintaining Homeostasis","volume":"14","year":"2025","journal-title":"J. Biomed. Pharm. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, Y.S. (2026). Immunometabolism in obesity: Understanding the beneficial and detrimental roles of inflammation. PLoS Biol., 24.","DOI":"10.1371\/journal.pbio.3003620"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1016\/j.immuni.2025.09.011","article-title":"Obesity, diabetes, and inflammation: Pathophysiology and clinical implications","volume":"58","author":"Donath","year":"2025","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/MED.0000000000000085","article-title":"Immune regulators of inflammation in obesity-associated type 2 diabetes and coronary artery disease","volume":"21","author":"Strissel","year":"2014","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vilari\u00f1o-Garc\u00eda, T., Polonio-Gonz\u00e1lez, M.L., P\u00e9rez-P\u00e9rez, A., Ribalta, J., Arrieta, F., Aguilar, M., Obaya, J.C., Gimeno-Orna, J.A., Iglesias, P., and Navarro, J. (2024). Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042338"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","article-title":"Myeloid-Derived Suppressor Cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3892\/ijo.2024.5667","article-title":"Impact of obesity-associated myeloid-derived suppressor cells on cancer risk and progression (Review)","volume":"65","author":"Garnacho","year":"2024","journal-title":"Int. J. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41577-020-00490-y","article-title":"Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity","volume":"21","author":"Veglia","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1182\/blood.V114.22.SCI-31.SCI-31","article-title":"Mechanism of Myeloid-Derived Suppressor Cell Differentiation in Cancer","volume":"114","author":"Gabrilovich","year":"2009","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, K., Wang, X., and Sun, N. (2025). Molecular mechanisms governing the differentiation and expansion of myeloid-derived suppressor cells. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1677201"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chaib, M., Chauhan, S.C., and Makowski, L. (2020). Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00351"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41416-018-0333-1","article-title":"Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression","volume":"120","author":"Groth","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9286","DOI":"10.3390\/cimb46090549","article-title":"Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review","volume":"46","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.2147\/ITT.S485642","article-title":"Emerging Role of MDSCS as Novel Biomarkers and Therapeutic Targets for Cancer Immunotherapy","volume":"14","year":"2025","journal-title":"Immunotargets Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.7150\/thno.105276","article-title":"Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: Targets and therapeutic strategies","volume":"15","author":"Wang","year":"2025","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/bs.acr.2015.04.002","article-title":"Myeloid-Derived Suppressor Cells: Critical Cells Driving Immune Suppression in the Tumor Microenvironment","volume":"128","author":"Parker","year":"2015","journal-title":"Adv. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s00262-010-0855-8","article-title":"Myeloid-derived suppressor cells: More mechanisms for inhibiting antitumor immunity","volume":"59","year":"2010","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40364-023-00475-8","article-title":"Myeloid-derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in hematological malignancies","volume":"11","author":"Wang","year":"2023","journal-title":"Biomark. Res."},{"key":"ref_19","first-page":"1","article-title":"Breast Cancer Immunology and Immunotherapy: Current Status and Future Perspectives","volume":"331","author":"Chiesa","year":"2017","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_20","first-page":"1","article-title":"Immunity, Hypoxia, and Metabolism-the Menage a Trois of Cancer: Implications for Immunotherapy","volume":"100","author":"Audige","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, Y.H., Li, C.Y., Liu, T., Dai, X.F., and Bazhin, A.V. (2020). Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01371"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14426","DOI":"10.1038\/s41598-021-93838-w","article-title":"Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer","volume":"11","author":"Chiesa","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002323","DOI":"10.1136\/jitc-2020-002323","article-title":"Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory\/relapsed diffuse large B-cell lymphoma: Translational results from the R2-GDP-GOTEL trial","volume":"9","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_24","first-page":"1","article-title":"Flow cytometry analysis of myeloid derived suppressor cells using 6 color labeling","volume":"190","year":"2024","journal-title":"Methods Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12150","DOI":"10.1038\/ncomms12150","article-title":"Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards","volume":"7","author":"Bronte","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1089\/vim.2021.0044","article-title":"Increased Blood Monocytic Myeloid Derived Suppressor Cells but Low Regulatory T Lymphocytes in Patients with Mild COVID-19","volume":"34","author":"Liro","year":"2021","journal-title":"Viral Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1002\/eji.201040895","article-title":"The biology of myeloid-derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity","volume":"40","author":"Youn","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.4103\/jcrt.JCRT_1222_20","article-title":"Immunosuppressive effects and mechanisms of three myeloid-derived suppressor cells subsets including monocytic-myeloid-derived suppressor cells, granulocytic-myeloid-derived suppressor cells, and immature-myeloid-derived suppressor cells","volume":"17","author":"Nagatani","year":"2021","journal-title":"J. Cancer Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4049\/jimmunol.1701019","article-title":"Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment","volume":"200","author":"Fenselau","year":"2018","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Du, J., and Shen, X. (2023). Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1157537"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1247135","DOI":"10.1080\/2162402X.2016.1247135","article-title":"The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells","volume":"5","author":"Lu","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"118975","DOI":"10.1016\/j.biopha.2026.118975","article-title":"High leptin levels independent of body mass index are associated with inflammation and poorer treatment response in patients with diffuse large B-cell lymphoma","volume":"195","year":"2026","journal-title":"Biomed. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Banerjee, D., and Mani, A. (2025). Obesity\u2019s systemic impact: Exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1681766"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1017\/S0029665122002671","article-title":"Inactivity and obesity: Consequences for macrophage-mediated inflammation and the development of cardiometabolic disease","volume":"82","author":"Bishop","year":"2023","journal-title":"Proc. Nutr. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"BSR20220200","DOI":"10.1042\/BSR20220200","article-title":"Adipose tissue macrophages and their role in obesity-associated insulin resistance: An overview of the complex dynamics at play","volume":"43","author":"Guria","year":"2023","journal-title":"Biosci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Karakasis, P., Stachteas, P., Iliakis, P., Sidiropoulos, G., Grigoriou, K., Patoulias, D., Antoniadis, A.P., and Fragakis, N. (2026). Inflammation and Resolution in Obesity-Related Cardiovascular Disease. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010535"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev-physiol-042222-024353","article-title":"Orchestration of the Adipose Tissue Immune Landscape by Adipocytes","volume":"86","author":"Bradley","year":"2024","journal-title":"Annu. Rev. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ghemis, L., Goriuc, A., Minea, B., Botnariu, G.E., Martu, M.A., Entuc, M., Cioloca, D., and Foia, L.G. (2024). Myeloid-Derived Suppressor Cells (MDSCs) and Obesity-Induced Inflammation in Type 2 Diabetes. Diagnostics, 14.","DOI":"10.3390\/diagnostics14212453"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.coi.2018.03.007","article-title":"Myeloid derived-suppressor cells: Their role in cancer and obesity","volume":"51","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/JLB.4HI0517-210R","article-title":"Frontline Science: High fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells","volume":"103","author":"Clements","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kiran, S., Kumar, V., Murphy, E.A., Enos, R.T., and Singh, U.P. (2021). High Fat Diet-Induced CD8(+) T Cells in Adipose Tissue Mediate Macrophages to Sustain Low-Grade Chronic Inflammation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.680944"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kiran, S., Rakib, A., Kodidela, S., Kumar, S., and Singh, U.P. (2022). High-Fat Diet-Induced Dysregulation of Immune Cells Correlates with Macrophage Phenotypes and Chronic Inflammation in Adipose Tissue. Cells, 11.","DOI":"10.3390\/cells11081327"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gambari, L., Cellamare, A., Grassi, F., Grigolo, B., Panciera, A., Ruffilli, A., Faldini, C., and Desando, G. (2023). Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119340"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Makki, K., Taront, S., Molendi-Coste, O., Bouchaert, E., Neve, B., Eury, E., Lobbens, S., Labalette, M., Duez, H., and Staels, B. (2014). Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092684"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104302","DOI":"10.1016\/j.cellimm.2021.104302","article-title":"Myeloid-derived suppressor cells (MDSC): When good intentions go awry","volume":"362","author":"Dean","year":"2021","journal-title":"Cell Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"Panwar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13045-024-01544-7","article-title":"Understanding the immunosuppressive microenvironment of glioma: Mechanistic insights and clinical perspectives","volume":"17","author":"Lin","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/prd.12384","article-title":"Myeloid-derived suppressor cells in obesity-associated periodontal disease: A conceptual model","volume":"87","author":"Kwack","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.2337\/db11-1506","article-title":"CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1\/M2 status","volume":"61","author":"Kitade","year":"2012","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chan, P.C., Lu, C.H., Chien, H.C., Tian, Y.F., and Hsieh, P.S. (2022). Adipose Tissue-Derived CCL5 Enhances Local Pro-Inflammatory Monocytic MDSCs Accumulation and Inflammation via CCR5 Receptor in High-Fat Diet-Fed Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214226"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1186\/s12964-024-01943-w","article-title":"The CCL5\/CCR5\/SHP2 axis sustains Stat1 phosphorylation and activates NF-kappaB signaling promoting M1 macrophage polarization and exacerbating chronic prostatic inflammation","volume":"22","author":"Jin","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/pedi.12388","article-title":"Insulitis in the pathogenesis of type 1 diabetes","volume":"17","author":"Pugliese","year":"2016","journal-title":"Pediatr. Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.clim.2014.04.006","article-title":"Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients","volume":"153","author":"Felton","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Burrack, A.L., Martinov, T., and Fife, B.T. (2017). T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00343"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, S., Tan, Q., Hou, Y., and Dou, H. (2021). Emerging Roles of Myeloid-Derived Suppressor Cells in Diabetes. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.798320"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, T.T., Lin, C.L., Chiang, M., He, J.T., Hung, C.H., and Hsieh, C.C. (2023). Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice. Cells, 12.","DOI":"10.3390\/cells12111507"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.4049\/jimmunol.0903636","article-title":"Myeloid-derived suppressor cells prevent type 1 diabetes in murine models","volume":"185","author":"Yin","year":"2010","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.2337\/db14-1868","article-title":"Reversal of New-Onset Type 1 Diabetes With an Agonistic TLR4\/MD-2 Monoclonal Antibody","volume":"64","author":"Bednar","year":"2015","journal-title":"Diabetes"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"470","DOI":"10.2337\/db21-0426","article-title":"Endosomal Sequestration of TLR4 Antibody Induces Myeloid-Derived Suppressor Cells and Reverses Acute Type 1 Diabetes","volume":"71","author":"Locker","year":"2022","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Grohova, A., Danova, K., Adkins, I., Sumnik, Z., Petruzelkova, L., Obermannova, B., Kolouskova, S., Spisek, R., and Palova-Jelinkova, L. (2020). Myeloid\u2014Derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0242092"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.1300654","article-title":"Reciprocal relationship between myeloid-derived suppressor cells and T cells","volume":"191","author":"Nagaraj","year":"2013","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mlynarska, E., Czarnik, W., Dzieza, N., Jedraszak, W., Majchrowicz, G., Prusinowski, F., Stabrawa, M., Rysz, J., and Franczyk, B. (2025). Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031094"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"23591","DOI":"10.1074\/jbc.M111.237123","article-title":"Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity","volume":"286","author":"Xia","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e230218","DOI":"10.1530\/EC-23-0218","article-title":"Decreased programmed cell death ligand 2-positive monocytic myeloid-derived suppressor cells and programmed cell death protein 1-positive T-regulatory cells in patients with type 2 diabetes: Implications for immunopathogenesis","volume":"12","author":"Liu","year":"2023","journal-title":"Endocr. Connect."},{"key":"ref_65","first-page":"442","article-title":"Type 2 Diabetes and its Impact on the Immune System","volume":"16","author":"Berbudi","year":"2020","journal-title":"Curr. Diabetes Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1038\/s41598-024-54496-w","article-title":"Increased monocytic myeloid-derived suppressor cells in type 2 diabetes correlate with hyperglycemic and was a risk factor of infection and tumor occurrence","volume":"14","author":"Zhou","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.1038\/s41598-026-37643-3","article-title":"The vasoprotective role of Myeloid-derived suppressor cells in pathogenesis of aortic dissection","volume":"16","author":"Xu","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.tem.2025.02.001","article-title":"Myeloid-derived suppressor cells in metabolic and cardiovascular disorders","volume":"36","author":"Yan","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/cvr\/cvw114","article-title":"CD11b+Gr-1+ myeloid-derived suppressor cells reduce atherosclerotic lesion development in LDLr deficient mice","volume":"111","author":"Foks","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/imm.13859","article-title":"CCR5-mediated homing of regulatory T cells and monocytic-myeloid derived suppressor cells to dysfunctional endothelium contributes to early atherosclerosis","volume":"173","author":"Akhtar","year":"2024","journal-title":"Immunology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bbrc.2017.10.150","article-title":"Effects of oral and subcutaneous administration of HSP60 on myeloid-derived suppressor cells and atherosclerosis in ApoE-\/- mice","volume":"498","author":"Hu","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Herrero-Fernandez, B., Gomez-Bris, R., Somovilla-Crespo, B., and Gonzalez-Granado, J.M. (2019). Immunobiology of Atherosclerosis: A Complex Net of Interactions. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215293"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.tem.2025.01.002","article-title":"Glucagon-like peptide-1 receptor agonism and end-organ protection","volume":"36","author":"Daniels","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1042\/CS20242825","article-title":"Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: A focus on diabetes and therapeutics","volume":"139","author":"Lee","year":"2025","journal-title":"Clin. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e18154","DOI":"10.7717\/peerj.18154","article-title":"Increased CD14(+)HLA-DR(-\/low) myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome","volume":"12","author":"Tan","year":"2024","journal-title":"PeerJ"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kologrivova, I., Dmitriukov, A., Naryzhnaya, N., Koshelskaya, O., Kharitonova, O., Vyrostkova, A., Kravchenko, E., Stepanov, I., Andreev, S., and Evtushenko, V. (2025). Associations Between Regulatory Immune Cells, Thymus Cellular Remodeling, and Vascular Aging in Advanced Coronary Atherosclerosis: A Pilot Study. Diagnostics, 15.","DOI":"10.3390\/diagnostics15192494"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"113","DOI":"10.5603\/aa.105599","article-title":"Monocytic myeloid-derived suppressor cells are more prevalent in patients treated with statins or with advanced carotid atherosclerosis requiring endarterectomy","volume":"31","author":"Zarobkiewicz","year":"2025","journal-title":"Acta Angiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000369696","article-title":"Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome","volume":"35","author":"Wang","year":"2015","journal-title":"Cell Physiol. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1161\/CIRCULATIONAHA.117.030811","article-title":"Cardioprotective Role of Myeloid-Derived Suppressor Cells in Heart Failure","volume":"138","author":"Zhou","year":"2018","journal-title":"Circulation"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ahmed, S.A., Ismail, H.M., Alahmedi, A.B., Alahmadi, F.B., Muhawish, A.F., Alsubhi, A.A., Almohammadi, Y.S., Alwusaidi, A.K., Alsaedi, A.S., and Alhazmi, T.G. (2025). Decoding the Inflammatory Pathway in Heart Failure: The Role of Interleukins and Tumor Necrosis Factor-Alpha in Disease Severity. J. Clin. Med., 14.","DOI":"10.3390\/jcm14176092"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Szabo, T.M., Frigy, A., and Nagy, E.E. (2021). Targeting Mediators of Inflammation in Heart Failure: A Short Synthesis of Experimental and Clinical Results. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313053"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Li, H., Chen, C., and Wang, D.W. (2021). Inflammatory Cytokines, Immune Cells, and Organ Interactions in Heart Failure. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.695047"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1007\/s11010-024-05112-y","article-title":"Myeloid-derived suppressor cells alleviate adverse ventricular remodeling after acute myocardial infarction","volume":"480","author":"Wang","year":"2025","journal-title":"Mol. Cell Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Anzai, A., Ko, S., and Fukuda, K. (2022). Immune and Inflammatory Networks in Myocardial Infarction: Current Research and Its Potential Implications for the Clinic. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095214"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"112965","DOI":"10.1016\/j.intimp.2024.112965","article-title":"Regulatory effect of rapamycin on recruitment and function of myeloid-derived suppressor cells in heart failure","volume":"141","author":"Yu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.humimm.2022.08.011","article-title":"Increased frequency of CD14(+)HLA-DR(-\/low) cells in type 2 diabetes patients with poor glycemic control","volume":"83","author":"Serrano","year":"2022","journal-title":"Hum. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.2147\/DMSO.S527411","article-title":"Role of Myeloid-Derived Suppressor Cells (MDSCs), Specifically Monocyte-Derived MDSCs, in Type 2 Diabetes-Related Diabetic Retinopathy","volume":"18","author":"Xiang","year":"2025","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Xing, Y.F., Cai, J.R., Qin, J.J., Zhou, W.Y., Li, C.M., and Li, X. (2020). Expansion of Monocytic Myeloid-Derived Suppressor Cells in Patients Under Hemodialysis Might Lead to Cardiovascular and Cerebrovascular Events. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.577253"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.immuni.2021.04.004","article-title":"MDSC: Markers, development, states, and unaddressed complexity","volume":"54","author":"Hegde","year":"2021","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"van Geffen, C., Heiss, C., Deissler, A., and Kolahian, S. (2022). Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.933847"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kawano, T., Shimamura, M., Nakagami, H., Kanki, H., Sasaki, T., and Mochizuki, H. (2019). Temporal and spatial profile of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in ischemic stroke in mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215482"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7872\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:13:58Z","timestamp":1788430438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":91,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177872"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177872","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}