Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler J. 2020;26(14):1816–21. https://doi.org/10.1177/1352458520970841.

Article  Google Scholar 

Hauser SL, Cree BAC. Treatment of multiple sclerosis: a review. Am J Med. 2020;133(12):1380–90. https://doi.org/10.1016/j.amjmed.2020.05.049.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu Z, Liao Q, Wen H, Zhang Y. Disease modifying therapies in relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis. Autoimmun Rev. 2021;20(6): 102826. https://doi.org/10.1016/j.autrev.2021.102826.

Article  CAS  PubMed  Google Scholar 

Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777–88. https://doi.org/10.1212/WNL.0000000000005347.

Article  PubMed  Google Scholar 

Callegari I, Derfuss T, Galli E. Update on treatment in multiple sclerosis. La Presse Médicale. 2021;50(2):104068. https://doi.org/10.1016/j.lpm.2021.104068.

Article  PubMed  Google Scholar 

Chalmer TA, Kalincik T, Laursen B, Sorensen PS, Magyari M, Sellebjerg F, et al. Treatment escalation leads to fewer relapses compared with switching to another moderately effective therapy. J Neurol. 2019;266:306–15. https://doi.org/10.1007/s00415-018-9126-y.

Article  PubMed  Google Scholar 

Merkel B, Butzkueven H, Traboulsee AL, Havrdova E, Kalincik T. Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: a systematic review. Autoimmun Rev. 2017;16(6):658–65. https://doi.org/10.1016/j.autrev.2017.04.010.

Article  PubMed  Google Scholar 

Mehling M, Kappos L, Derfuss T. Fingolimod for multiple sclerosis: mechanism of action, clinical outcomes, and future directions. Curr Neurol Neurosci Rep. 2011;11:492–7. https://doi.org/10.1007/s11910-011-0216-9.

Article  PubMed  Google Scholar 

Bascuñana P, Möhle L, Brackhan M, Pahnke J. Fingolimod as a treatment in neurologic disorders beyond multiple sclerosis. Drugs R D. 2020;20:197–207. https://doi.org/10.1007/s40268-020-00316-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Antel J. Mechanisms of action of fingolimod in multiple sclerosis. Clin Exp Neuroimmunol. 2014;5(1):49–54. https://doi.org/10.1111/cen3.12079.

Article  CAS  Google Scholar 

Sáenz-Cuesta M, Alberro A, Muñoz-Culla M, Osorio-Querejeta I, Fernandez-Mercado M, Lopetegui I, et al. The first dose of fingolimod affects circulating extracellular vesicles in multiple sclerosis patients. Int J Mol Sci. 2018;19(8):2448. https://doi.org/10.3390/ijms19082448.

Article  CAS  PubMed Central  Google Scholar 

Kuhle J, Disanto G, Dobson R, Adiutori R, Bianchi L, Topping J, et al. Conversion from clinically isolated syndrome to multiple sclerosis: a large multicantre study. Mult Scler. 2015;21(8):1013–24. https://doi.org/10.1177/1352458514568827.

Article  CAS  PubMed  Google Scholar 

Arvin AM, Wolinsky JS, Kappos L, Morris MI, Reder AT, Tornatore C, et al. Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management. JAMA Neurol. 2015;72(1):31–9. https://doi.org/10.1001/jamaneurol.2014.3065.

Article  PubMed  PubMed Central  Google Scholar 

Teniente-Serra A, Hervás JV, Quirant-Sánchez B, Mansilla MJ, Grau-López L, Ramo-Tello C, et al. Baseline differences in minor lymphocyte subpopulations may predict response to fingolimod in relapsing-remitting multiple sclerosis patients. CNS Neurosci Ther. 2016;22(7):584–92. https://doi.org/10.1111/cns.12548.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quirant-Sánchez B, Hervás-García JV, Teniente-Serra A, Brieva L, Moral-Torres E, Cano A, et al. Predicting therapeutic response to fingolimod treatment in multiple sclerosis patients. CNS Neurosci Ther. 2018;24(12):1175–84. https://doi.org/10.1111/cns.12851.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quirant-Sánchez B, Presas-Rodriguez S, Mansilla MJ, Teniente-Serra A, Hervás-García JV, Brieva L, et al. Th1Th17CM lymphocyte subpopulation as a predictive biomarker of disease activity in multiple sclerosis patients under dimethyl fumarate or fingolimod treatment. Mediat Inflamm. 2019. https://doi.org/10.1155/2019/8147803.

Article  Google Scholar 

Moreno-Torres I, González-García C, Marconi M, García-Grande A, Rodríguez-Esparragoza L, Elvira V, et al. Immunophenotype and transcriptome profile of patients with multiple sclerosis treated with fingolimod: setting up a model for prediction of response in a 2-year translational study. Front Immunol. 2018. https://doi.org/10.3389/fimmu.2018.01693.

Article  PubMed  PubMed Central  Google Scholar 

Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7(1):12150. https://doi.org/10.1038/ncomms12150.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Millrud CR, Bergenfelz C, Leandersson K. On the origin of myeloid-derived suppressor cells. Oncotarget. 2017;8(2):3649–65. https://doi.org/10.18632/oncotarget.12278.

Article  PubMed  Google Scholar 

Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21:485–98. https://doi.org/10.1038/s41577-020-00490-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kuchroo VK, et al. CD11b+ Ly-6Chi suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol. 2007;179(8):5228–37. https://doi.org/10.4049/jimmunol.179.8.5228.

Article  CAS  PubMed  Google Scholar 

Mishra MK, Wang J, Silva C, MacK M, Yong VW. Kinetics of proinflammatory monocytes in a model of multiple sclerosis and its perturbation by laquinimod. Am J Pathol. 2012;181(2):642–51. https://doi.org/10.1016/j.ajpath.2012.05.011.

Article  CAS  PubMed  Google Scholar 

Moliné-Velázquez V, Ortega MC, Vila del Sol V, Melero-Jerez C, de Castro F, Clemente D. The synthetic retinoid Am 80 delays recovery in a model of multiple sclerosis by modulating myeloid-derived suppressor cell fate and viability. Neurobiol Dis. 2014;67:149–64. https://doi.org/10.1016/j.nbd.2014.03.017.

Article  CAS  PubMed  Google Scholar 

Melero-Jerez C, Alonso-Gómez A, Moñivas E, Lebrón-Galán R, Machín-Díaz I, de Castro F, et al. The proportion of myeloid-derived suppressor cells in the spleen is related to the severity of the clinical course and tissue damage extent in a murine model of multiple sclerosis. Neurobiol Dis. 2020;140: 104869. https://doi.org/10.1016/j.nbd.2020.104869.

Article  CAS  PubMed  Google Scholar 

Liu G, Bi Y, Wang R, Yang H, Zhang Y, Wang X, et al. Targeting S1P1 receptor protects against murine immunological hepatic injury through myeloid-derived suppressor cells. J Immunol. 2014;192(7):3068–79. https://doi.org/10.4049/jimmunol.1301193.

Article  CAS  PubMed  Google Scholar 

Li Y, Zhou T, Wang Y, Ning C, Lv Z, Han G, et al. The protumorigenic potential of FTY720 by promoting extramedullary hematopoiesis and MDSC accumulation. Oncogene. 2017;36:3760–71. https://doi.org/10.1038/onc.2017.2.

Article  CAS  PubMed  Google Scholar 

Asakura T, Ishii M, Namkoong H, Suzuki S, Kagawa S, Yagi K, et al. Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b+Gr-1+ cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary emphysema. Mucosal Immunol. 2018;11:1606–20. https://doi.org/10.1038/s41385-018-0077-5.

Article  CAS  PubMed  Google Scholar 

Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, Takehara K, et al. FTY720 ameliorates murine sclerodermatous chronic graft-versus-host disease by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin. Arthritis Rheum. 2013;65(6):1624–35. https://doi.org/10.1002/art.37933.

Article  CAS  Google Scholar 

Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age review-article. Nat Immunol. 2018;19:108–19. https://doi.org/10.1038/s41590-017-0022-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ioannou M, Alissafi T, Lazaridis I, Deraos G, Matsoukas J, Gravanis A, et al. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol. 2012;192(3):1334. https://doi.org/10.4049/jimmunol.1390073.

Article  CAS  Google Scholar 

Iacobaeus E, Douagi I, Jitschin R, Marcusson-Ståhl M, Andrén AT, Gavin C, et al. Phenotypic and functional alterations of myeloid-derived suppressor cells during the disease course of multiple sclerosis. Immunol Cell Biol. 2018;96(8):820–30. https://doi.org/10.1111/imcb.12042.

Article  CAS  PubMed  Google Scholar 

Cantoni C, Cignarella F, Ghezzi L, Mikesell B, Bollman B, Berrien-Elliott MM, et al. Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol. 2017;133:61–77. https://doi.org/10.1007/s00401-016-1621-6.

Article  CAS  PubMed  Google Scholar 

Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, et al. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol. 2004;153(1–2):108–21. https://doi.org/10.1016/j.jneuroim.2004.04.015.

Article  CAS  PubMed  Google Scholar 

Colombo E, Di Dario M, Capitolo E, Chaabane L, Newcombe J, Martino G, et al. Fingolimod may support neuroprotection via blockade of astrocyte nitric oxide. Ann Neurol. 2014. https://doi.org/10.1002/ana.24217.

Article  PubMed