Watch Dr Steensma outline how the immune system works differently in HR-MDS
- TIM-3 may play a role in the innate and adaptive immune dysfunction of HR-MDS and AML4-8
- This immune dysfunction allows LSCs and blasts to evade immune detection and over-proliferate4-8
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David Steensma, MD, Global Hematology Head,
Transitional Clinical Oncology, Novartis Institute for Biomedical Research, United States
Immune dysfunction inhibits the ability of immune cells to kill malignant myeloid cells, such as LSCs and blasts1-3
Increase in immune
suppressive cells
(Tregs, M2 macrophages)9,12
Decrease in
cytotoxic cells
(T cells, NK cells) and DC1-3
Cytotoxic cells
cannot kill malignant
myeloid cells
(LSCs, leukemic blasts)1
- Immune dysfunction causes macrophages to increase anti-inflammatory signaling and leaves T cells, NK cells, and dendritic cells unable to kill malignant myeloid cells such as LSCs and blasts2,3,9
- Leukemic stem cells and blasts are then able to multiply and spread throughout the bone marrow4,5
- This immune dysfunction is complicated by the fact that patients are often older with already suppressed immune systems10,11
TIM-3 expression may be a key driver of immune dysfunction7,8
- TIM-3 is expressed on LSCs, blasts, and dysfunctional immune cells involved in innate and adaptive immunity7,8
- TIM-3 expression levels increase from low-risk MDS to high-risk MDS to AML13
- This suggests an important role for TIM-3 in immune dysfunction associated with these diseases7,8,13
Immune dysfunction remains unaddressed in HR-MDS and AML, and current treatments continue to fall short in closing the durability gap14,15
- Currently available treatments for HR-MDS and AML only target LSCs, and durable responses remain elusive14,15
- Research into immune targets, such as TIM-3, is underway