TIGIT: An important inhibitor of antitumor response

TIGIT is a new target being explored as part of the next era of cancer immunotherapy research. TIGIT inhibits the body’s antitumor response and interrupts cancer-immunity processes.^2,3

TIGIT disrupts the cancer immune response by:

Suppressing T cell–mediated tumor killing^1,4
Altering T-cell differentiation^1,4
Inhibiting natural killer cell–mediated tumor killing^1,4

Inducing immunosuppressive dendritic cells^1,4

An attractive novel target to help restore immune response^3,4

Expressed on tumor-infiltrating T cells and natural killer cells, which are the primary drivers of antitumor response⁴
Plays a role in a variety of solid and hematologic malignancies, including lung and esophageal cancers^3,4

Targeting both TIGIT and PD-L1 may augment the antitumor immune response seen with PD-L1 inhibition alone^5-7

TIGIT and PD-L1 independently interact with CD226 and converge to block the costimulatory signal⁷

TIGIT is a co-inhibitory immune checkpoint that blocks antitumor response^1-5

TIGIT dampens the immune response by competing with its costimulatory counterpart, CD226, for binding to PVR, therefore blocking the activating signal and impairing T-cell function. PD-1 activation also disrupts the activation of CD226. Complementary inhibition of TIGIT and PD-L1 restores CD226 signaling and antitumor immune response.^5-7

Targeting TIGIT and PD-L1 may amplify antitumor response^5-7

In preclinical studies, complementary inhibition enhanced immune-mediated response against tumor cells⁸

Simultaneous inhibition of TIGIT and PD-L1 pathways led to improved T-cell effector function^3,9
PD-L1 inhibition was amplified with complementary inhibition of TIGIT^5,7,9,10

Complementary inhibition of TIGIT and PD-L1 is being explored across a range of cancer types, including lung and esophageal³

Dual targeting of TIGIT and PD-L1 may amplify the anti-tumor effects seen with inhibiting PD-L1 alone, representing a promising research approach for areas of unmet need^1-3,5-7

CD226=cluster of differentiation 226; PD-1=programmed death receptor-1; PD-L1=programmed death-ligand 1; PVR=polio virus receptor; TIGIT=T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain.

References:

Manieri NA, Chiang EY, Grogan JL. TIGIT: a key inhibitor of the cancer immunity cycle. Trends Immunol. 2017;38(1):20-28.
Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint. Clin Exp Immunol. 2019;200(2):108-119.
Ge Z, Peppelenbosch MP, Sprengers D, Kwekkeboom J. TIGIT, the next step towards successful combination immune checkpoint therapy in cancer. Front Immunol. 2021;12:699895. doi:10.3389/fimmu.2021.699895
Rotte A, Sahasranaman S, Budha N. Targeting TIGIT for immunotherapy of cancer: update on clinical development. Biomedicines. 2021:9(9):1277. doi:10.3390/biomedicines9091277
Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957
Pauken KE, Wherry EJ. TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit. Cancer Cell. 2014;26(6):785-787.
Banta KL, Xu X, Chitre AS, et al. Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. Immunity. 2022;55(3):512-526.e9. doi:10.1016/j.immuni.2022.02.005
Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol. 2022;19(1):37-50.
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.
Rodriguez-Abreu D, Johnson ML, Hussein M, et al. CITYSCAPE: primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab plus atezolizumab versus placebo plus atezolizumab as 1L treatment in patients with PD-L1-selected NSCLC. Presented at: ASCO Annual Meeting; May 15, 2020; Chicago, IL, US.
Chiang EY, Mellman I. TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy. J Immunother Cancer. 2022;10(4):e004711. doi:10.1136/jitc-2022-004711

R.E. Pharm E De Bruyne - M-BE-00002521 - created on 24/11/2023

TIGIT is a new target being explored as part of the next era of cancer immunotherapy research. TIGIT inhibits the body’s antitumor response and interrupts cancer-immunity processes.2,3

TIGIT disrupts the cancer immune response by:

An attractive novel target to help restore immune response3,4

Targeting both TIGIT and PD-L1 may augment the antitumor immune response seen with PD-L1 inhibition alone5-7

TIGIT is a co-inhibitory immune checkpoint that blocks antitumor response1-5

Targeting TIGIT and PD-L1 may amplify antitumor response5-7

In preclinical studies, complementary inhibition enhanced immune-mediated response against tumor cells8