{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:29:19Z","timestamp":1767698959421,"version":"3.48.0"},"reference-count":88,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-30011"],"award-info":[{"award-number":["19-74-30011"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian state-funded project for ICBFM SB RAS","award":["125012300659-6"],"award-info":[{"award-number":["125012300659-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that strongly suppress immunity and expand during tumor progression. Various antitumor chemotherapy agents can induce MDSC accumulation, reducing treatment effectiveness. We investigated the impact of the CHOP regimen and its components (cyclophosphamide (CTX), doxorubicin, vincristine, and prednisolone) on the dynamics of MDSC accumulation and the associated changes in immune cell profiles in the peripheral blood and spleen of healthy and lymphosarcoma RLS40-bearing CBA mice. CHOP induced significant thymic atrophy and splenomegaly, T-cell depletion, and robust accumulation of MDSCs, primarily polymorphonuclear MDSCs. Kinetic analysis in healthy mice revealed splenic MDSC expansion and T-cell depletion peaked 10-day post-CHOP, driven mainly by CTX; whereas doxorubicin, vincristine, and prednisolone exerted minimal immunological effects. To mitigate CTX-induced MDSCs, glycyrrhizic acid (GLZ), a natural triterpenoid with known immunomodulatory properties, and febroxolone methyl (FM), its novel cyano enone derivative, were administered to CTX-treated mice. GLZ significantly attenuated splenic MDSC accumulation, partially restored T-cell function, and improved immune organ morphology. Conversely, FM exacerbated immunosuppression by expanding MDSCs, enhancing their function by upregulation of Nos1 and Ido1 in vivo, and promoting the generation of highly immunosuppressive bone marrow-derived MDSCs in vitro. Thus, our results highlight CTX\u2019s central role in CHOP-induced MDSC expansion. The structure-dependent duality of triterpenoids, countering (GLZ) or promoting (FM) MDSC expansion, offers therapeutic potential for pathologies ranging from chemotherapy-induced side effects to autoimmunity.<\/jats:p>","DOI":"10.3390\/ijms27020564","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclophosphamide-Mediated Induction of Myeloid-Derived Suppressor Cells In Vivo: Kinetics of Accumulation, Immune Profile, and Immunomodulation by Oleanane-Type Triterpenoids"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2075-2599","authenticated-orcid":false,"given":"Mona S.","family":"Awad","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician Lavrentyev Ave. 8, 630090 Novosibirsk, Russia"},{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogova Str. 2, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5729-9910","authenticated-orcid":false,"given":"Aleksandra V.","family":"Sen\u2019kova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician Lavrentyev Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-9555","authenticated-orcid":false,"given":"Andrey V.","family":"Markov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician Lavrentyev Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5316-790X","authenticated-orcid":false,"given":"Oksana V.","family":"Salomatina","sequence":"additional","affiliation":[{"name":"N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Academician Lavrentyev Ave., 9, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-1049","authenticated-orcid":false,"given":"Marina A.","family":"Zenkova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician Lavrentyev Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-1890","authenticated-orcid":false,"given":"Oleg V.","family":"Markov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician Lavrentyev Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, C., Liu, T., Dai, X., and Bazhin, A. (2020). V 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_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/cytob.21206","article-title":"Complexity and challenges in defining myeloid-derived suppressor cells","volume":"88","author":"Damuzzo","year":"2015","journal-title":"Cytom. Part B-Clin. Cytom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s10555-006-9002-6","article-title":"Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer","volume":"25","author":"Kusmartsev","year":"2006","journal-title":"Cancer Metastasis Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbcan.2014.04.003","article-title":"Signaling pathways involved in MDSC regulation","volume":"1846","author":"Trikha","year":"2014","journal-title":"Biochim. Biophys. Acta-Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.18632\/oncotarget.12278","article-title":"On the origin of myeloid-derived suppressor cells","volume":"8","author":"Millrud","year":"2016","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.coi.2010.01.021","article-title":"Myeloid-derived suppressor cell heterogeneity and subset definition","volume":"22","author":"Peranzoni","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.4049\/jimmunol.181.8.5791","article-title":"Subsets of myeloid-derived suppressor cells in tumor-bearing mice","volume":"181","author":"Youn","year":"2008","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nri3175","article-title":"Coordinated regulation of myeloid cells by tumours","volume":"12","author":"Gabrilovich","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12672-023-00793-1","article-title":"Regulation of T cells by myeloid-derived suppressor cells: Emerging immunosuppressor in lung cancer","volume":"14","author":"He","year":"2023","journal-title":"Discov. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Huang, J., Zhao, Y., Zhao, K., Yin, K., and Wang, S. (2023). Function of reactive oxygen species in myeloid-derived suppressor cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1226443"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41392-021-00670-9","article-title":"Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.imbio.2014.07.017","article-title":"Myeloid regulatory cells in tumor spreading and metastasis","volume":"220","author":"Keskinov","year":"2015","journal-title":"Immunobiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev-med-051013-052304","article-title":"Regulation of Tumor Metastasis by Myeloid-derived Suppressor Cells","volume":"66","author":"Condamine","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E566","DOI":"10.1073\/pnas.1424927112","article-title":"Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils","volume":"112","author":"Casbon","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00262-014-1591-2","article-title":"Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer","volume":"63","author":"Idorn","year":"2014","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e005025","DOI":"10.1136\/jitc-2022-005025","article-title":"Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer","volume":"10","author":"Henick","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, B., Wang, Z., Wu, L., Zhang, M., Li, W., Ding, J., Zhu, J., Wei, H., and Zhao, K. (2013). Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057114"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Toor, S.M., Syed Khaja, A., El Salhat, H., Bekdache, O., Kanbar, J., Jaloudi, M., and Elkord, E. (2016). Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00560"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5661","DOI":"10.1158\/1078-0432.CCR-15-3104","article-title":"Clinical significance of circulating CD33+CD11b+HLA-DR\u2212 myeloid cells in patients with stage IV melanoma treated with Ipilimumab","volume":"22","author":"Kanterman","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s00262-013-1475-x","article-title":"Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients","volume":"62","author":"Jordan","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1053\/j.gastro.2008.03.020","article-title":"A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T Cells","volume":"135","author":"Hoechst","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/08820139.2017.1407787","article-title":"High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients","volume":"47","author":"Elwan","year":"2018","journal-title":"Immunol. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9518","DOI":"10.1158\/0008-5472.CAN-07-0175","article-title":"Dynamics of the immune reaction to pancreatic cancer from inception to invasion","volume":"67","author":"Clark","year":"2007","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1258504","DOI":"10.1080\/2162402X.2016.1258504","article-title":"CD13hi Neutrophil-like myeloid-derived suppressor cells exert immune suppression through Arginase 1 expression in pancreatic ductal adenocarcinoma","volume":"6","author":"Zhang","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00262-011-1178-0","article-title":"Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth","volume":"61","author":"Porembka","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alban, T.J., Bayik, D., Otvos, B., Rabljenovic, A., Leng, L., Jia-Shuin, L., Roversi, G., Lauko, A., Momin, A.A., and Mohammadi, A.M. (2020). Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01191"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/14737140.2022.2030227","article-title":"Myeloid-derived suppressor cells: A grey eminence in the AML tumor microenvironment ?","volume":"22","author":"Bewersdorf","year":"2022","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1158\/0008-5472.CAN-07-6611","article-title":"A history of cancer chemotherapy","volume":"68","author":"DeVita","year":"2008","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1056\/NEJMoa011795","article-title":"CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma","volume":"346","author":"Coiffier","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1056\/NEJM199304083281404","article-title":"Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced Non-Hodgkin\u2019s lymphoma","volume":"328","author":"Fisher","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/JBM.S190784","article-title":"How the discovery of rituximab impacted the treatment of B-cell non-Hodgkin\u2019s lymphomas","volume":"10","author":"Mohammed","year":"2019","journal-title":"J. Blood Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S1470-2045(11)70235-2","article-title":"CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diff use large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group","volume":"12","author":"Pfreundschuh","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.intimp.2009.03.015","article-title":"Gemcitabine directly inhibits myeloid derived suppressor cells in BALB\/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice","volume":"9","author":"Le","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.4049\/jimmunol.1202781","article-title":"Anti-tumor effect of paclitaxel is mediated by inhibition of MDSCs and chronic inflammation in the spontaneous melanoma model","volume":"190","author":"Sevko","year":"2013","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1158\/0008-5472.CAN-09-3690","article-title":"5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity","volume":"70","author":"Vincent","year":"2010","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100224","DOI":"10.1016\/j.jhepr.2020.100224","article-title":"Chemotherapy-induced recruitment of myeloid-derived suppressor cells abrogates efficacy of immune checkpoint blockade","volume":"3","author":"Kwong","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1182\/blood-2004-06-2410","article-title":"Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide","volume":"105","author":"Lutsiak","year":"2005","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/CJI.0b013e318255585a","article-title":"Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors","volume":"35","year":"2012","journal-title":"J. Immunother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"106932","DOI":"10.1016\/j.intimp.2020.106932","article-title":"Glycyrrhizic acid facilitates anti-tumor immunity by attenuating Tregs and MDSCs: An immunotherapeutic approach","volume":"88","author":"Juin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1158\/1078-0432.CCR-09-3272","article-title":"Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer","volume":"16","author":"Nagaraj","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Markov, A.V., Sen\u2019kova, A.V., Babich, V.O., Odarenko, K.V., Talyshev, V.A., Salomatina, O.V., Salakhutdinov, N.F., Zenkova, M.A., and Logashenko, E.B. (2020). Dual effect of soloxolone methyl on LPS-induced inflammation in vitro and in vivo. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217876"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1476-4598-13-30","article-title":"Preclinical evidences toward the use of triterpenoid CDDO-Me for solid cancer prevention and treatment","volume":"13","author":"Wang","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.intimp.2011.01.007","article-title":"Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions","volume":"11","author":"Zhou","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_45","first-page":"3292","article-title":"Swertianolin ameliorates immune dysfunction in sepsis via blocking the immunosuppressive function of myeloid-derived suppressor cells","volume":"65","author":"Ren","year":"2021","journal-title":"Eur. J. Histochem. EJH"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"464","DOI":"10.4049\/jimmunol.172.1.464","article-title":"Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer","volume":"172","author":"Nefedova","year":"2004","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e004384","DOI":"10.1136\/jitc-2021-004384","article-title":"STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice","volume":"10","author":"Bitsch","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Su, Y.L., Banerjee, S., White, S.V., and Kortylewski, M. (2018). STAT3 in tumor-associated myeloid cells: Multitasking to disrupt immunity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061803"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e70001","DOI":"10.1111\/sji.70001","article-title":"The impact of cytokines and tumour-conditioned medium on the properties of murine in vitro generated myeloid-derived suppressor cells","volume":"101","author":"Awad","year":"2025","journal-title":"Scand. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00430-010-0151-4","article-title":"Subsets, expansion and activation of myeloid-derived suppressor cells","volume":"199","author":"Ribechini","year":"2010","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1182\/blood.V95.1.212","article-title":"Nitric oxide-producing CD11b+Ly-6G(Gr-1)+CD31(ER-MP12)+cells in the spleen of cyclophosphamide-treated mice: Implications for T-cell responses in immunosuppressed mice","volume":"95","author":"Angulo","year":"2000","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1158\/0008-5472.CAN-13-3596","article-title":"Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis","volume":"74","author":"Ding","year":"2014","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00262-008-0523-4","article-title":"Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy","volume":"58","author":"Salem","year":"2009","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e954471","DOI":"10.4161\/21624011.2014.954471","article-title":"Chemotherapy-induced myeloid suppressor cells and antitumor immunity: The Janus face of chemotherapy in immunomodulation","volume":"3","author":"Ding","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.urology.2008.07.031","article-title":"Multiplex analysis of urinary cytokine levels in a rat model of cyclophosphamide-induced cystitis","volume":"73","author":"Smaldone","year":"2009","journal-title":"Urology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1152\/physiolgenomics.00117.2001","article-title":"Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis","volume":"9","author":"Malley","year":"2002","journal-title":"Physiol. Genom."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e350","DOI":"10.1097\/HS9.0000000000000350","article-title":"Beyond DNA damage: Exploring the immunomodulatory effects of cyclophosphamide in multiple myeloma","volume":"4","author":"Swan","year":"2020","journal-title":"HemaSphere"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.intimp.2011.12.016","article-title":"IFN-\u03b3 producing T cells contribute to the increase of myeloid derived suppressor cells in tumor-bearing mice after cyclophosphamide treatment","volume":"12","author":"Guo","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00262-012-1343-0","article-title":"Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo","volume":"62","author":"Tongu","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1476-4598-13-158","article-title":"Anti-tumor innate immunity activated by intermittent metronomic cyclophosphamide treatment of 9L brain tumor xenografts is preserved by anti-angiogenic drugs that spare VEGF receptor 2","volume":"13","author":"Doloff","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00262-018-2288-8","article-title":"The effect of everolimus and low-dose cyclophosphamide on immune cell subsets in patients with metastatic renal cell carcinoma: Results from a phase I clinical trial","volume":"68","author":"Huijts","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/jid.2012.444","article-title":"Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents antitumor response in melanoma","volume":"133","author":"Sevko","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00262-015-1781-6","article-title":"A randomized phase II clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer","volume":"65","author":"Noguchi","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cellimm.2012.03.010","article-title":"Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide","volume":"276","author":"Salem","year":"2012","journal-title":"Cell. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1158\/0008-5472.CAN-13-1545","article-title":"Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer","volume":"74","author":"Alizadeh","year":"2014","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23824","DOI":"10.1038\/srep23824","article-title":"Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2","volume":"6","author":"Rong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13703","DOI":"10.1111\/jcmm.15928","article-title":"Methylprednisolone alleviates multiple sclerosis by expanding myeloid-derived suppressor cells via glucocorticoid receptor \u03b2 and S100A8\/9 up-regulation","volume":"24","author":"Wang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/cmi.2017.5","article-title":"Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1 \u03b1-dependent glycolysis","volume":"15","author":"Lu","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"114705","DOI":"10.1016\/j.biopha.2023.114705","article-title":"A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes","volume":"162","author":"Song","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.intimp.2018.06.005","article-title":"Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders","volume":"61","author":"Salminen","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/nutraceuticals4030022","article-title":"Effects of ursolic acid on colorectal cancer: A review of recent evidence","volume":"4","author":"Kornel","year":"2024","journal-title":"Nutraceuticals"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.1158\/1078-0432.CCR-08-0040","article-title":"Prevention and treatment of experimental estrogen receptor\u2013negative mammary carcinogenesis by the synthetic triterpenoid CDDO-methyl ester and the rexinoid LG100268","volume":"14","author":"Liby","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100058","DOI":"10.1016\/j.medidd.2020.100058","article-title":"Analysis of glycyrrhizin binding to protein HMGB1","volume":"7","author":"Vergoten","year":"2020","journal-title":"Med. Drug Discov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s10020-023-00717-3","article-title":"HMGB1 and Toll-like receptors: Potential therapeutic targets in autoimmune diseases","volume":"29","author":"Ren","year":"2023","journal-title":"Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15625","DOI":"10.1038\/s41598-021-94928-5","article-title":"Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury","volume":"11","author":"Oh","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/jcmm.14703","article-title":"Glycyrrhizin mitigates radiation-induced acute lung injury by inhibiting the HMGB1\/TLR4 signalling pathway","volume":"24","author":"Zheng","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_77","first-page":"5175","article-title":"Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT\/mTOR\/STAT3 signaling","volume":"8","author":"He","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1158\/0008-5472.CAN-07-3036","article-title":"Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)\u2192signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3","volume":"68","author":"Ahmad","year":"2008","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9886","DOI":"10.1038\/s41598-017-06907-4","article-title":"A unique tolerizing dendritic cell phenotype induced by the synthetic triterpenoid CDDO-DFPA (RTA-408) is protective against EAE","volume":"7","author":"Wei","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1158\/1940-6207.CAPR-10-0197","article-title":"Synthetic Triterpenoids Prolong Survival in a Transgenic Mouse Model of Pancreatic Cancer","volume":"3","author":"Liby","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3109\/00365521.2010.516450","article-title":"Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function","volume":"46","author":"Hu","year":"2011","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bmc.2013.10.049","article-title":"Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells","volume":"22","author":"Salomatina","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11541","DOI":"10.1016\/j.tet.2008.10.035","article-title":"Chemical modifications of natural triterpenes\u2014Glycyrrhetinic and boswellic acids: Evaluation of their biological activity","volume":"64","author":"Rao","year":"2008","journal-title":"Tetrahedron"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1134\/S0026893318020073","article-title":"Novel Glycyrrhetinic Acid Derivative Soloxolone Methyl Inhibits the Inflammatory Response and Tumor Growth In Vivo","volume":"52","author":"Markov","year":"2018","journal-title":"Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., and Emerson, M. (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000411"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1196\/annals.1378.090","article-title":"Animal model of drug-resistant tumor progression","volume":"1091","author":"Mironova","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sounbuli, K., Alekseeva, L.A., Markov, O.V., and Mironova, N.L. (2023). A Comparative Study of Different Protocols for Isolation of Murine Neutrophils from Bone Marrow and Spleen. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417273"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:14:23Z","timestamp":1767698063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":88,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020564"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020564","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]}}}