Masahiro Ogasawara, Mamiko Miyashita, Yuka Yamagishi, Shuichi Ota
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Impact of Reduction in Myeloid-derived Suppressor Cells by Wilms’ Tumor 1-targeted Dendritic Cell Vaccines on Clinical Outcomes in Acute Leukemia Patients
Background
Myeloid-derived suppressor cells (MDSCs) play a critical role in immunotherapy.
Methods
We investigated the effects of the Wilms' tumor 1 (WT1) peptide-loaded dendritic cell (DC) vaccination on MDSCs in patients with acute leukemia.
Results
WT1-DC vaccination reduced MDSCs and enhanced WT1-specific immunity. In complete remission patients, MDSC reduction was accompanied by decreased arginase 1 and indoleamine 2,3-dioxygenase levels and increased interleukin (IL)-12 and interferon-γ levels in plasma. Conversely, patients with disease progression showed increased IL-10 and transforming growth factor-β1. Reduced MDSCs were correlated with WT1-specific immune activation and associated with longer survival.
Conclusion
These findings indicate that WT1-DC vaccination suppresses MDSCs and improves clinical outcomes.
Clinical Trial Registration
This study is registered with the University Hospital Medical Information Network (UMIN) in Japan (Registration ID: UMIN000027279).
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