Iannis Aifantis, Ph.D.
2019 Funding recipient
Single-cell mapping of the evolving immune microenvironment during MDS to AML transition
Discovery Research Grant 2019
Myelodysplastic syndrome (MDS) is a pre-cancerous disease of the blood, which progresses to the more aggressive acute myeloid leukemia (AML) in approximately 30% of cases. MDS currently affects about 60,000 people in the US, and about 10,000 new cases are diagnosed each year. Life expectancy for MDS patients ranges from 5 months to 3 years, yet therapeutic options for MDS patients are limited.
In recent years, advances in understanding of the immune system have led to a major breakthrough in cancer therapy, with the development of immunotherapy drugs that target the immune system rather than the cancer cells. These drugs are effective in many types of cancer, and have revolutionized treatment for cancers that were often considered untreatable in the past. The effectiveness of immunotherapeutic drugs arises from their mode of action: instead of targeting the cancerous cells, they act by activating the immune system and driving it to target the tumor. Currently, established immunotherapies have yielded modest results in MDS/AML, and they are not offered to patients.
We have mapped the composition and status of the immune system in different stages of MDS and AML, at high resolution, using advanced genomic technologies. We have characterized inflammatory processes in MDS and AML patients that affect the T- and B-cell mediated immune response to the disease. We have derived a risk score based on the inflammatory state, that can refine patient assignment to treatment regimens. Our data can help improve patient risk stratification.
Muto T, Guillamot M, Yeung J, Fang J, Bennett J, Nadorp B, Lasry A, Redondo LZ, Choi K, Gong Y, et al., TRAF6 Functions as a Tumor Suppressor in Myeloid Malignancies by Directly Targeting MYC Oncogenic Activity, Cell Stem Cell, 2022, 29 (2), 298-314.e9 DOI: 10.1016/j.stem.2021.12.007.
Yeaton A, Cayanan G, Loghavi S, Dolgalev I, Leddin EM, Loo CE, Torabifard H, Nicolet D, Wang J, Corrigan K, et al., The Impact of Inflammation-Induced Tumor Plasticity during Myeloid Transformation, Cancer Discovery, 2022, CD-21-1146 DOI: 10.1158/2159-8290.CD-21-1146.