This site is intended for
US
Healthcare Professionals only.

For Patients
 

TIGIT

Diagram of TIGIT pathway expressed between a T cell and tumor cell

T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), an immune checkpoint receptor, can suppress T-cell activation and promote T-cell exhaustion. Inhibition of TIGIT may increase cytotoxic T-cell proliferation and function.

  • TIGIT is an immune checkpoint receptor on cytotoxic, memory, and Tregs, as well as NK
    cells
    1,2
    • On cytotoxic T cells and NK cells, interaction of TIGIT with either of its 2 ligands, CD155 (PVR) and CD112 (Nectin2), suppresses immune activation1,2
    • When TIGIT is expressed on Tregs, however, this interaction enhances their ability to suppress the immune response3
  • The suppressive effect of TIGIT is counterbalanced by the immune-activating receptor CD226 (also called DNAM1), which is also expressed on cytotoxic T cells and NK cells and competes with TIGIT to bind to CD155 and CD1124,5
    • The inhibitory signal provided by TIGIT overpowers DNAM1’s ability to stimulate T-cell activation5
  • In cancer, tumor cells exploit the inhibitory TIGIT pathway to avoid immune-mediated destruction
  • Based on preclinical studies, inhibition of TIGIT alone or in combination with other checkpoint inhibitors increases the proliferation and function of cytotoxic T cells7,9-11
Thumbnail for the How Does TIGIT Overpower Cytotoxic T-Cell Activity video Thumbnail for the How Does TIGIT Overpower Cytotoxic T-Cell Activity video

How does TIGIT overpower cytotoxic T-cell activity?

Learn more about TIGIT, an immune checkpoint receptor

Watch video

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

REFERENCES–TIGIT

1. Yu X, Harden K, Gonzalez LC, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48-57. 2. Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42):17858-17863. 3. Joller N, Lozano E, Burkett PR, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40(4):569-581. 4. Bottino C, Castriconi R, Pende D, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198(4):557-567. 5. Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 axis regulates human T cell function. J Immunol. 2012;188(8):3869-3875. 6. Goding SR, Wilson KA, Xie Y, et al. Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol. 2013;190(9):4899-4909. 7. Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell. 2014;26(6):923-937. 8. Chauvin J-M, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest. 2015;125(5):2046-2058. 9. Joller N, Hafler JP, Brynedal B, et al. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J Immunol. 2011;186(3):1338-1342. 10. Hung AL, Maxwell R, Theodros D, et al. TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. Oncoimmunology. 2018;7(8):e1466769. doi:10.1080/2162402X.2018. 1466769. 11. Kurtulus S, Sakuishi K, Ngjow S-F, et al. J Clin Invest. 2015;125(11):4053-4062.