From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

Comont, T.; Treiner, Emmanuel; Vergez, François

doi:10.3390/diagnostics11111982

Cited by 6 publications

(3 citation statements)

References 186 publications

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“…The pathogenesis of MDS is largely unclear. Studies suggest that immune dysregulation and autoimmunity in early disease stages leads to bone marrow failure and proliferation of malignant myeloid precursors in later stages [ 5 ]′ [ 72 ]. This wide immune landscape and absence of distinct immune classification complicates immune targeting with available agents and development of vaccination strategies.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Vaccines: a promising therapy for myelodysplastic syndrome

Gera,

Chauhan,

Castillo

et al. 2024

J Hematol Oncol

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Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole cell-based vaccines and dendritic cell-based vaccines. These therapeutic vaccines have shown acceptable safety profiles, but consistent clinical responses remain elusive despite robust immunological reactions. Combining vaccines with immunotherapeutic agents holds promise and requires further investigation. Herein, we highlight therapeutic vaccine trials while reviewing challenges and future directions of successful vaccination strategies in MDS.

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Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Vaccines: a promising therapy for myelodysplastic syndrome

Gera,

Chauhan,

Castillo

et al. 2024

J Hematol Oncol

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“…Data regarding the efficacy of using these inhibitors in hematologic malignancies are limited to mouse models and in vitro studies. 9 , 17 , 18 This is not a minor issue, as allogeneic hematopoietic stem cell transplantation (HSCT), the only curative treatment available, 19 is rarely feasible for most CMML patients. 20 , 21 In addition, hypomethylating agents, the only approved therapy, have dismal response rates in the MP subtype.…”

Section: Introductionmentioning

confidence: 99%

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Hurtado-Navarro,

Cuenca-Zamora,

Zamora

et al. 2023

Cell Reports Medicine

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“…Monitoring the immune system at the time of MDS diagnosis could therefore be very helpful to more precisely assess the stage of the disease and the inherent risk of progression to AML for each case of MDS, in addition to current prognosis models based on cytogenetic and mutational data. Finally, deep characterization of deregulated immune pathways could also offer perspectives for the use of immunomodulatory drugs in some subtypes of MDS specifically adapted to the patient’s immune status as already recently reviewed [ 13 ], and this will probably lead to the development of new targeted therapies. Here, we therefore review the different immune dysregulations which can be detected during the course of MDS, i.e., from the MDS precursor conditions (CHIP, CCUS, ICUS) to their leukemic progression.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

Simoni

Chapuis

2022

Diagnostics

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Myelodysplastic syndromes (MDS) constitute a very heterogeneous group of diseases with a high prevalence in elderly patients and a propensity for progression to acute myeloid leukemia. The complexity of these hematopoietic malignancies is revealed by the multiple recurrent somatic mutations involved in MDS pathogenesis and the paradoxical common phenotype observed in these patients characterized by ineffective hematopoiesis and cytopenia. In the context of population aging, the incidence of MDS will strongly increase in the future. Thus, precise diagnosis and evaluation of the progression risk of these diseases are imperative to adapt the treatment. Dysregulations of both innate and adaptive immune systems are frequently detected in MDS patients, and their critical role in MDS pathogenesis is now commonly accepted. However, different immune dysregulations and/or dysfunctions can be dynamically observed during the course of the disease. Monitoring the immune system therefore represents a new attractive tool for a more precise characterization of MDS at diagnosis and for identifying patients who may benefit from immunotherapy. We review here the current knowledge of the critical role of immune dysfunctions in both MDS and MDS precursor conditions and discuss the opportunities offered by the detection of these dysregulations for patient stratification.

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From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

Cited by 6 publications

References 186 publications

Vaccines: a promising therapy for myelodysplastic syndrome

Vaccines: a promising therapy for myelodysplastic syndrome

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

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