The Role of T Cells and Myeloid-derived Suppressor Cells in Refractory Immune Thrombocytopenia

Overview

Journal Br J Haematol

Specialty Hematology

Date 2023 Sep 22

PMID 37735552

Authors

Karina Yazdanbakhsh

Drew Provan

John W Semple

Affiliations

Soon will be listed here.

Abstract

Immune thrombocytopenia (ITP) is characterized by a dysregulated immune response against platelets, affecting both their destruction and production. A role for an abnormal T-cell compartment has been established in ITP pathogenesis and treatments that increase platelet counts in patients with ITP have shown improvements in T-cell profiles. On the other hand, patients who were refractory to treatment appear to retain the T-cell abnormalities as before. Myeloid-derived suppressive cells (MDSCs) are also emerging as key contributors to the immune pathology of ITP and response to treatment. In this review, we will discuss how various treatments affect the T-cell and MDSC compartments in ITP. The review will focus on studies that have examined the underlying mechanisms and/or genetic basis responsible for refractoriness to a given treatment and highlight remaining challenges in identifying factors and mechanisms to predict response to treatment.

Citing Articles

The intersection of epigenetics and immune thrombocytopenia: new insights into disease mechanisms and treatments.

Zhou X, Shan N Mol Biol Rep. 2025; 52(1):257.

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The miR-641-STIM1 and SATB1 axes play important roles in the regulation of the Th17/Treg balance in ITP.

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References

Zhang G, Yang P, Liu X, Liu H, Wang J, Wang J . HMGB1 is increased in patients with immune thrombocytopenia and negatively associates with Tregs. Thromb Res. 2022; 213:128-136. DOI: 10.1016/j.thromres.2022.02.021. View

Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A . The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol. 2015; 16(7):737-45. DOI: 10.1038/ni.3194. View

Hou Y, Xie J, Wang S, Li D, Wang L, Wang H . Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia. Cell Mol Immunol. 2022; 19(7):764-776. PMC: 9243139. DOI: 10.1038/s41423-022-00859-0. View

Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L . Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 2007; 13(7):828-35. PMC: 2135607. DOI: 10.1038/nm1609. View

Veglia F, Sanseviero E, Gabrilovich D . Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021; 21(8):485-498. PMC: 7849958. DOI: 10.1038/s41577-020-00490-y. View

Wang S, Zhang X, Leng S, Xu Q, Sheng Z, Zhang Y . Immune Checkpoint-Related Gene Polymorphisms Are Associated With Primary Immune Thrombocytopenia. Front Immunol. 2021; 11:615941. PMC: 7874092. DOI: 10.3389/fimmu.2020.615941. View

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold D . Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2008; 113(11):2386-93. DOI: 10.1182/blood-2008-07-162503. View

Timilshina M, You Z, Lacher S, Acharya S, Jiang L, Kang Y . Activation of Mevalonate Pathway via LKB1 Is Essential for Stability of T Cells. Cell Rep. 2019; 27(10):2948-2961.e7. DOI: 10.1016/j.celrep.2019.05.020. View

Mouzaki A, Theodoropoulou M, Gianakopoulos I, Vlaha V, Kyrtsonis M, Maniatis A . Expression patterns of Th1 and Th2 cytokine genes in childhood idiopathic thrombocytopenic purpura (ITP) at presentation and their modulation by intravenous immunoglobulin G (IVIg) treatment: their role in prognosis. Blood. 2002; 100(5):1774-9. View

10.

Monzon Manzano E, Alvarez Roman M, Justo Sanz R, Fernandez Bello I, Hernandez D, Martin Salces M . Platelet and immune characteristics of immune thrombocytopaenia patients non-responsive to therapy reveal severe immune dysregulation. Br J Haematol. 2020; 189(5):943-953. DOI: 10.1111/bjh.16459. View

11.

Stimpson M, Wolf J, Williams E, Lait P, Schewitz-Bowers L, Greenwood R . CD4 T cells from patients with glucocorticoid-refractory immune thrombocytopenia have altered cytokine expression. Br J Haematol. 2021; 196(4):1113-1117. DOI: 10.1111/bjh.17884. View

12.

Chow L, Aslam R, Speck E, Kim M, Cridland N, Webster M . A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood. 2009; 115(6):1247-53. DOI: 10.1182/blood-2009-09-244772. View

13.

Sabatini D . Twenty-five years of mTOR: Uncovering the link from nutrients to growth. Proc Natl Acad Sci U S A. 2017; 114(45):11818-11825. PMC: 5692607. DOI: 10.1073/pnas.1716173114. View

14.

Zhang J, Ma D, Zhu X, Qu X, Ji C, Hou M . Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica. 2009; 94(9):1326-9. PMC: 2738732. DOI: 10.3324/haematol.2009.007823. View

15.

Wang T, He X, Ran N, Liu C, Xing L, Wang H . Immunological characteristics and effect of cyclosporin in patients with immune thrombocytopenia. J Clin Lab Anal. 2021; 35(9):e23922. PMC: 8418498. DOI: 10.1002/jcla.23922. View

16.

Audia S, Mahevas M, Nivet M, Ouandji S, Ciudad M, Bonnotte B . Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments. Hemasphere. 2021; 5(6):e574. PMC: 8171374. DOI: 10.1097/HS9.0000000000000574. View

17.

Wang S, Zhang X, Leng S, Zhang Y, Li J, Peng J . SIRT1 single-nucleotide polymorphisms are associated with corticosteroid sensitivity in primary immune thrombocytopenia patients. Ann Hematol. 2021; 100(10):2453-2462. DOI: 10.1007/s00277-021-04583-z. View

18.

Sheng Z, Li J, Wang Y, Li S, Hou M, Peng J . A CARD9 single-nucleotide polymorphism rs4077515 is associated with reduced susceptibility to and severity of primary immune thrombocytopenia. Ann Hematol. 2019; 98(11):2497-2506. DOI: 10.1007/s00277-019-03796-7. View

19.

Ni X, Wang L, Wang H, Yu T, Xie J, Li G . Low-dose decitabine modulates myeloid-derived suppressor cell fitness via LKB1 in immune thrombocytopenia. Blood. 2022; 140(26):2818-2834. DOI: 10.1182/blood.2022016029. View

20.

Aslam R, Burack W, Segel G, McVey M, Spence S, Semple J . Intravenous immunoglobulin treatment of spleen cells from patients with immune thrombocytopenia significantly increases the percentage of myeloid-derived suppressor cells. Br J Haematol. 2017; 181(2):262-264. DOI: 10.1111/bjh.14542. View