Azacitidine improves the T-cell repertoire in patients with myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia

Fozza, Claudio; Corda, G; Barraqueddu, Francesca; Virdis, Patrizia; Contini, Salvatore; Galleu, Antonio; Isoni, Antonella; Dore, Fausto; Angelucci, Emanuele; Longinotti, M

doi:10.1016/j.leukres.2015.06.007

Cited by 33 publications

(15 citation statements)

References 40 publications

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“…Patients with MDS or AML who responded well to treatment with azacitidine demonstrated decreased skewing of the TCR CDR3 profile as assessed by spectratyping [64]. A similar result was observed in four patients with solid tumors treated with decitabine on a clinical trial protocol who demonstrated increased TCR diversity and lower abundancies of expanded clones in comparison to pre-treatment levels [65].…”

Section: Modulation Of Immune Cell Subsets By Hypomethylating Agentsmentioning

confidence: 75%

Immunological effects of hypomethylating agents

Lindblad

Goswami

Hourigan

et al. 2017

Expert Review of Hematology

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Introduction: Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert Commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

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Section: Modulation Of Immune Cell Subsets By Hypomethylating Agentsmentioning

confidence: 75%

Immunological effects of hypomethylating agents

Lindblad

Goswami

Hourigan

et al. 2017

Expert Review of Hematology

View full text Add to dashboard Cite

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“…The presence of a dominant peak with a relative intensity greater than 50% of the total peak area is usually used to specifically identify oligoclonal subfamilies (panel E) in the degree of CDR3 skewing in their T-cell repertoire involving both CD4+ and CD8+ cells. Altered TCR repertoire patterns have already been shown to characterize different malignancies [2][3][4][5] and to be potentially reversible after anti-neoplastic treatment [14]. In more details, a similar pattern has been recently demonstrated in patients with non Hodgkin lymphomas [3], while in different disorders, such as myelodysplastic syndromes, the increased degree of skewing was confined to the CD8+ subset [4].…”

Section: To the Editormentioning

confidence: 64%

Evidence of a skewed T‐cell repertoire in patients with light chain amyloidosis

Fozza

Corda

Barraqueddu

et al. 2016

Hematological Oncology

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“…In a different study of 11 patients treated with azacytidine, responses of their autoimmune disorders were achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively . Noteworthy, we very recently demonstrated that most of the T‐cell abnormalities observed in MDS patients tend to revert during therapy with azacytidine, especially within the CD4+ subset …”

Section: Response Of Autoimmune Manifestations To Therapies For Mdsmentioning

confidence: 87%

“…99 Noteworthy, we very recently demonstrated that most of the T-cell abnormalities observed in MDS patients 120 tend to revert during therapy with azacytidine, especially within the CD4+ subset. 121 Also allogeneic SCT has been able to restore autoimmune disorders in some patients with MDS. The condition most often reported in this field was BD, which was resolved after cord blood SCT in 3 patients [107][108][109] and after peripheral blood SCT in 1 patient.…”

Section: Other Organs and Conditionsmentioning

confidence: 99%

The burden of autoimmunity in myelodysplastic syndromes

Fozza

2017

Hematological Oncology

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The clinical history of patients with myelodysplastic syndromes (MDS) is characterised by bone marrow insufficiency as well as by the possible evolution into acute leukaemia. However a number of reports highlight the frequent occurrence of autoimmune manifestations involving different sites and organs. The present review will first describe the clinical pictures most often observed in MDS patients. The actual burden of autoimmunity will be then addressed by focusing on the few available registry studies. Finally, the potential collateral impact of specific treatments for MDS on the evolution of autoimmune disorders will be considered.

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Azacitidine improves the T-cell repertoire in patients with myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia

Cited by 33 publications

References 40 publications

Immunological effects of hypomethylating agents

Immunological effects of hypomethylating agents

Evidence of a skewed T‐cell repertoire in patients with light chain amyloidosis

The burden of autoimmunity in myelodysplastic syndromes

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