Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes

Sand, Kristoffer; Theorell, Jakob; Bruserud, Øystein; Bryceson, Yenan T.; Kittang, Astrid Olsnes

doi:10.1007/s00262-016-1865-y

Cited by 8 publications

(9 citation statements)

References 43 publications

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“…After recognition of tumor antigens presented by tumor cells through their MHC class I, activated CD8 + T cells release cytotoxic molecules leading to tumor cell apoptosis [ 96 ]. In the BM of MDS patients, a decrease in CD8 + T-cell cytotoxicity has been observed [ 97 , 98 ]. This loss of cytotoxicity is confirmed by the observation of an exhausted-like phenotype of bone marrow CD8 + T cells in MDS.…”

Section: Abnormal Immune Cell Repartition And/or Functions During The...mentioning

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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Section: Abnormal Immune Cell Repartition And/or Functions During The...mentioning

confidence: 99%

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

Simoni

Chapuis

2022

Diagnostics

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“…MDS blasts in high-risk diseases overexpress PD-L1 in comparison to normal controls [ 78 ] and this can be further augmented by the effects of cytokines, such as TNF-a, and IFN-γ, which induce PD-1 and PD-L1 expression, on T-cells and MDS cells, respectively [ 79 ]. Interestingly, Sand et al reported increased numbers of BM cytotoxic T-cells; however, they were accompanied by dysfunctional T-cell receptor (TCR) cytotoxicity [ 80 ].…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Barakos

Hatzimichael

2022

Diseases

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Bone marrow, besides the known functions of hematopoiesis, is an active organ of the immune system, functioning as a sanctuary for several mature immune cells. Moreover, evidence suggests that hematopoietic stem cells (the bone marrow’s functional unit) are capable of directly sensing and responding to an array of exogenous stimuli. This chronic immune stimulation is harmful to normal hematopoietic stem cells, while essential for the propagation of myeloid diseases, which show a dysregulated immune microenvironment. The bone marrow microenvironment in myelodysplastic syndromes (MDS) is characterized by chronic inflammatory activity and immune dysfunction, that drive excessive cellular death and through immune evasion assist in cancer cell expansion. Acute myeloid leukemia (AML) is another example of immune response failure, with features that augment immune evasion and suppression. In this review, we will outline some of the functions of the bone marrow with immunological significance and describe the alterations in the immune landscape of MDS and AML that drive disease progression.

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“…Drugs widely used for MDS have lately been shown to affect T‐cell polarization, which may suggest effects on MDSCs activity. Azacitidine, the drug of choice in high‐risk MDS, has been shown to affect T‐cell polarization in the Th17/Treg‐axis in high‐risk MDS and to influence levels of BM CD57 + T‐cells, CD57 + T‐cell degranulation and CD34 + BM cell directed cytotoxicity 34,35 . Specific MDSC‐targeting in MDS has so far been aiming at CD33‐expressing cells 36 .…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

“…Azacitidine, the drug of choice in high-risk MDS, has been shown to affect T-cell polarization in the Th17/Treg-axis in high-risk MDS and to influence levels of BM CD57 + T-cells, CD57 + T-cell degranulation and CD34 + BM cell directed cytotoxicity. 34,35 Specific MDSC-targeting in MDS has so far been aiming at CD33-expressing cells. 36 So far, BI 836858 (Fc-engineered anti-CD33 moAb) for antibody-dependent cell-mediated cytotoxicity by NK-cells is currently tested in MDS patients in an ongoing Phase I/II clinical trial (ClinicalTrials.gov Identifier: NCT02240706).…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets

et al. 2019

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Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.

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Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes

Cited by 8 publications

References 43 publications

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets

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