It's time to see both sides of TIM-3

TIM-3 expression may provide an opportunity for dual impact by suppressing (turning down) leukemic cell proliferation and activating (turning up) immune response.1,2

 

Take a closer look at HD-MDS and AML in this video

Learn more about what patients and health care professionals face with these conditions.

The TIM-3 receptor is expressed on immune cells as well as leukemic stem cells (LSCs) and blast cells but not on normal hematopoietic stem cells.3-9

  • TIM-3 is a key regulator of innate and adaptive immune responses10
TIM-3 receptor expression on leukemic stem cells, immune cells, and hematopoietic stem cells

 

 

 

Activate immune response and suppress leukemic cell proliferation

 

Opportunity to activate (turn up) immune response

  • When TIM-3 binds to its cognate ligand, components of the immune response may be suppressed1,2,9
  • Based on preclinical models, preventing TIM-3 from fulfilling this function could limit these effects and increase an antitumor immune response3

Opportunity to suppress (turn down) leukemic cell proliferation

  • TIM-3 is preferentially expressed on LSCs and blast cells, which enables these cells to overproliferate and evade detection by the immune system1,8,9

 

 

 

Clinical significance has not yet been established and research is ongoing.

 

Watch a video about

The role of TIM-3

Go further in-depth on the role and opportunity of TIM-3 in HR-MDS and AML

 

 

TIME to Look Closer

Novartis is researching the role of TIM-3 in HR-MDS and AML.

AML, acute myeloid leukemia; HR-MDS, high-risk myelodysplastic syndrome; TIM-3, T cell immunoglobulin and mucin domain-3.

References: 1. 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. 2. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, 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. 3. Hastings WD, Anderson DE, Kassam N. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur J Immunol. 2009;39(9):2492-2501. 4. Ndhlovu LC, Lopez-Vergès S, Barbour JD, et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood. 2012;119(16):3734-3743. 5. Zhang Y, Ma CJ, Wang JM, et al. Tim‐3 regulates pro‐ and anti‐inflammatory cytokine expression in human CD14+ monocytes. J Leukoc Biol. 2012;91(2):1891-96. 6. Nakayama M, Akiba H, Takeda K, et al. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood. 2009;113(16):3821-3830. 7. 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. 8. Kikushige Y, Shima T, Takayanagi S, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010;7(6):708-717. 9. Asayama T, Tamura H, Ishibashi M. 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. Das M, Zhu C, Kuchroo V. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017;276(1):97-111.

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