This site is intended for
Healthcare Professionals only.

For Patients


Diagram of TIM-3 pathway expressed between an inactive T cell and a tumor cell

T-cell immunoglobulin mucin-3 (TIM-3), an immune checkpoint receptor, can suppress effector T-cell activity and is associated with T-cell and natural killer (NK)-cell exhaustion. Inhibition may boost innate and adaptive immune responses.

  • T-cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint receptor that is expressed on a wide variety of immune cells, including cytotoxic T cells, regulatory T cells (Tregs), natural killer (NK) cells, and some antigen-presenting cells (APCs) such as dendritic cells (DCs)1,2
    • TIM-3 interacts with numerous ligands such as phosphatidylserine (PS), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), galectin-9, and high mobility group box 1 (HMGB1)1,3
      • On apoptotic cells, PS can impair T-cell function4
        • PS or HMGB1 interactions with TIM-3 on tumor-infiltrating DCs may lead to impaired ability of DCs to activate T cells and promote inflammation4-6
      • On cytotoxic T cells, TIM-3 binding to galectin-9 on immunosuppressive
        MDSCs can enhance MDSC expansion and suppressor activity1,7
      • T-cell expression of TIM-3 and its co-expression with CEACAM1 correlate with T-cell exhaustion1,8,9
  • TIM-3 suppresses both innate and adaptive immune cells1,6
    • TIM-3 can indirectly suppress effector T-cell activity by acting on myeloid-derived suppressor cells (MDSCs), Tregs, and DCs1,7,10
  • TIM-3 expression on Tregs can reduce T-cell function and proliferation10
  • Increased TIM-3 expression on NK cells has also been linked to NK-cell exhaustion1,11
    • Additionally, NK cell–expressed TIM-3 can interact with PS or galectin-9 to promote NK cell dysfunction1,11,12
  • Preclinical data suggest that TIM-3 blockade can rescue NK-cell activity, promote tumor antigen processing, and reinvigorate exhausted T cells to restore their proliferation and function1,8,11
  • TIM-3 is often co-expressed with other immune checkpoint receptors, and preclinical studies indicate that co-blockade of TIM-3 with another immune checkpoint receptor may further reinvigorate exhausted T cells8,14,15

Get I-O Resources

Order or download
educational tools for your
patients and practice

See all resources

Clinical Trials

Learn more about our
current clinical trials

Learn more


1. Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989-1004. 2. Han G, Chen G, Shen B, Li Y. Tim-3: an activation marker and activation limiter of innate immune cells. Front Immunol. 2013;4:449. doi:10.3389/fimmu.2013.00449. 3. Nakayama M, Akiba H, Takeda K, et al. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood. 2009;113(16):3821-3830. 4. Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH. TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev. 2010;235(1):172-189. 5. Maurya N, Gujar R, Gupta M, Yadav V, Verma S, Sen P. Immunoregulation of dendritic cells by the receptor T cell Ig and mucin protein-3 via Bruton's tyrosine kinase and c-Src. J Immunol. 2014;193(7):3417-3425. 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. Dardalhon V, Anderson AC, Karman J, et al. Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. J Immunol. 2010;185(3):1383-1392. 8. Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207(10):2175-2186. 9. Zhang Y, Cai P, Li L, et al. Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients. Int Immunopharmacol. 2017;43:210-218. 10. Gautron A-S, Dominguez-Villar M, de Marcken M, Hafler DA. Enhanced suppressor function of TIM-3+FoxP3+ regulatory T cells. Eur J Immunol. 2014;44(9):2703-2711. 11. da Silva IP, Gallois A, Jimenez-Baranda S, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2(5):410-422. 12. Weber JK, Zhou R. Phosphatidylserine-induced conformational modulation of immune cell exhaustion-associated receptor TIM3. Sci Rep. 2017;7:13579. doi:10.1038/s41598-017-14064-x. 13. Anderson AC. Tim-3: an emerging target in the cancer immunotherapy landscape. Cancer Immunol Res. 2014;2(5):393-398. 14. Lee J, Ahn E, Kissick HT, Ahmed R. Reinvigorating exhausted T cells by blockade of the PD-1 pathway. For Immunopathol Dis Therap. 2015;6(1-2):7-17. 15. 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.