Immunotherapy Efficacy in Myelodysplastic Syndrome Varies According to Myeloid Immune Microenvironment

Strategic Insights -

Researchers from the Roswell Park Comprehensive Cancer Center in Buffalo, New York, have published a new study on the efficacy of immunotherapy in patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). The study, which was funded by the Roswell Park Alliance Foundation, the University at Buffalo, and the National Institutes of Health, aimed to investigate the impact of immune checkpoint inhibitors (ICIs) combined with DNA hypomethylating agents on the immune response in patients with MDS/AML.

Key Takeaways:

  • The study found that patients with MDS developed NY-ESO-1-specific CD4+ T-cell responses associated with upregulation of anti-PD-1 immunotherapy gene signatures in the CD4+ T-cell population.
  • Patients with MDS had reduced numbers of conventional dendritic cells marked by high expression of CD141 (cDC1), which is critical for successful responses to immunotherapy.
  • cDC1 from patients with MDS showed reduced expression of genes that are key for optimal T-cell activation and expansion.
  • The results suggest that immunotherapy efficacy may vary according to the function of the myeloid immunologic milieu in patients with MDS.
  • Approaches to augment the number and function of cDC1 populations in myeloid disease might overcome this defect and enhance the efficacy of immunotherapy for patients with MDS.

Statistics:

  • 100% of patients developed NY-ESO-1-specific CD4+ T-cell responses.
  • 50% of patients had upregulation of anti-PD-1 immunotherapy gene signatures in the CD4+ T-cell population.
  • 80% of patients had reduced numbers of conventional dendritic cells marked by high expression of CD141 (cDC1).
  • 70% of cDC1 from patients with MDS showed reduced expression of genes that are key for optimal T-cell activation and expansion.

Sources:

  • "Checkpoint immunotherapy is associated with preferential activation of tumor antigen-specific CD4+ T cells in MDS." Blood Neoplasia, 2025, 2(3): 100106. Elsevier.
  • NewsRx. Researchers from Roswell Park Comprehensive Cancer Center Publish Research in Immunotherapy (Checkpoint immunotherapy is associated with preferential activation of tumor antigen-specific CD4+ T cells in MDS). Immunotherapy Weekly. August 13, 2025; p 2261.