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MDS 2023 | The role and targeting of immune dysregulation in MDS

Uwe Platzbecker, MD, University of Leipzig, Leipzig, Germany, discusses immune dysregulation in patients with myelodysplastic syndromes (MDS). Prof. Platzbecker explains the differences in immune dysregulation across patients with low- and high-risk MDS and notes ongoing efforts to understand the role of immune deficits in the treatment and prognostication of MDS. Prof. Platzbecker further highlights potential treatment avenues for immune dysregulation in MDS, such as inflammasome inhibitors. This interview took place at the 17th International Congress on Myelodysplastic Syndromes (MDS) 2023, held in Marseille, France.

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Transcript (edited for clarity)

I think we have clear evidence for an immune dysregulation in MDS, across all subtypes of MDS, a more inflammatory state in lower risk MDS patients also including pyroptosis as in basically concept explaining also peripheral cytopenia of these patients whereas in the high risk MDS setting including also secondary AML, the more immunosuppressive state has been observed with regulatory T cells for instance being increased...

I think we have clear evidence for an immune dysregulation in MDS, across all subtypes of MDS, a more inflammatory state in lower risk MDS patients also including pyroptosis as in basically concept explaining also peripheral cytopenia of these patients whereas in the high risk MDS setting including also secondary AML, the more immunosuppressive state has been observed with regulatory T cells for instance being increased. The question but still is, although we know quite well that these kind of inflammatory or immunosuppressive states do exist, the question is are they culprit or bystander and are they also druggable? If so, does that change the prognosis of these patients? And also, does it basically, not only change the prognosis, but also improve the level of cytopenia? I think at the moment there are a lot of efforts to better understand the role of these kind of changes of the immune system, innate or acquired in MDS and whether they can be intervened with specific agents or drugs, including also inflammasome inhibitors which just entered early clinical stage development.

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