Focusing on TIM-3 expression may help address the immune dysfunction in HR-MDS and AML

Focusing on TIM-3 expression may help address the immune dysfunction in HR-MDS and AML

Focusing on TIM-3 expression may help address the immune dysfunction in HR-MDS and AML

Focusing on TIM-3 expression may help address the immune dysfunction in HR-MDS and AML

Watch Dr Platzbecker discuss the role of TIM-3 in immune dysfunction

 
  • “TIM-3 may be an interesting target for immuno-myeloid therapy in higher-risk MDS and AML.”
    —Uwe Platzbecker, MD, PhD
  • TIM-3 may play an important role in immune dysfunction1,2
  • Addressing TIM-3 expression may help reawaken immune function
 
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Uwe Platzbecker, MD, PhD, Director of Medical Clinic I,
Hematology and Cell Therapy University Hospital, Leipzig, Germany

 

TIM-3 is expressed on dysfunctional immune cells involved in innate and adaptive immunity1,3

T Cell
(Immune Cell)

NK Cell
(Immune Cell)

Macrophage
(Immune Cell)

Dendritic Cell
(Immune Cell)

Monocyte
(Immune Cell)

WILL ADDRESSING IMMUNE DYSFUNCTION CONTRIBUTE TO CLOSING THE DURABILITY GAP IN HR-MDS AND AML?

 

TIM-3 expression may play a critical role in the suppression of cells involved in innate and adaptive immunity4-8

  • TIM-3 is expressed on exhausted T cells, can impair NK cells and DCs, and is associated with dysfunctional macrophages and monocytes4-8
  • This may cause immune cells to be unable to kill LSCs and blasts
CAN FOCUSING ON TIM-3 EXPRESSION HELP REAWAKEN THE IMMUNE SYSTEM IN HR-MDS AND AML?

 

TIM-3 is also expressed on LSCs and blasts, but not on healthy hematopoietic stem cells2

Leukemic Blast Cell

Leukemic Stem Cell

Healthy Stem Cell

  • There is evidence that TIM-3 delivers proliferative signals when expressed on MDS blasts9
  • TIM-3 signaling may be critical for the maintenance of AML10
LEARN MORE ABOUT THE DURABILITY GAP IN HR-MDS AND AML

 

TIM-3 expression has been associated with disease severity and progression to AML9,10

TIM-3 expression on immune and myeloid cells increases with disease severity
TIM-3 expression on immune and myeloid cells increases with disease severity
 
  • TIM-3 expression levels increase from low-risk MDS to high-risk MDS to AML9
  • Data suggest that TIM-3 signaling may play a critical role in progression of MDS to AML10
LEARN MORE ABOUT IMMUNE DYSFUNCTION IN HR-MDS AND AML

 

 

Learn more about the role of TIM-3 in HR-MDS and AML with this interactive video

 
 
 

AML, acute myeloid leukemia; DCs, dendritic cells; HR-MDS, higher-risk myelodysplastic syndromes; LR-MDS, lower-risk myelodysplastic syndromes; LSCs, leukemic stem cells; MDS, myelodysplastic syndromes; NK, natural killer; OS, overall survival; NSCLC, non-small cell lung cancer; NK, natural killer; TIM-3, T cell immunoglobulin and mucin domain-3.

 
References: 1. Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536-541. 2. Kikushige Y, Shima T, Takayanagi S-I, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010;7(6):708-717. 3. da Silva I, Gallois A, Jiminez-Baranda S, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2(5):410-422. 4. Sakuishi K, Apetoh L, Sullivan JM, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187-2194. 5. Silva IG, Yasinska IM, Sakhnevych SS, et al. The Tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells. EBioMedicine. 2017;22:44-57. 6. Chiba S, Baghdadi M, Akiba H, et al. Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13(9):832-842. 7. Yan W, Liu X, Ma H, et al. Tim-3 fosters HCC development by enhancing TGF-β-mediated alternative activation of macrophages. Gut. 2015;64(10):1593-1604. 8. Zhang Y, Ma CJ, Wang JM, et al. Tim-3 negatively regulates IL-12 expression by monocytes in HCV infection. PLoS One. 2011;6(5):e19664. doi:10.1371/journal.pone.0019664. 9. Asayama T, Tamura H, Ishibashi M, et al. Functional expression of Tim-3 on blasts and clinical impact of its ligand galectin-9 in myelodysplastic syndromes. Oncotarget. 2017;8(51):88904-88917. 10. Kikushige Y, Miyamoto T, Yuda J, et al. A TIM-3/Gal-9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemic progression. Cell Stem Cell. 2015;17(3):341-352.