Skip To Main Content

PD-L1 + TIGIT

Discover what's next in cancer immunotherapy research

Explore one of the promising new targets

See how TIGIT Works

TIGIT is a co-inhibitory immune checkpoint that blocks antitumor response1-3

Novel target

A novel target that may help restore immune response4,5

  • Expressed on tumor-infiltrating T cells and natural killer cells, which are the primary drivers of antitumor response
  • Plays a role in a variety of solid malignancies
Cancer immune response

TIGIT disrupts the cancer immune response by1,4:

  • Suppressing T cell–mediated tumor killing
  • Altering T-cell differentiation
  • Inhibiting natural killer cell–mediated tumor killing
  • Inducing immunosuppressive dendritic cells
TIGIT and PD-L1 complementary inhibition

Targeting both TIGIT and PD-L1 may enhance the antitumor immune response seen with PD-L1 inhibition alone2,6,7

  • TIGIT and PD-L1 independently interact with CD226 and converge to block the co-stimulatory signal
  • PD-1 activation also disrupts the activation of CD226
  • Complementary inhibition of TIGIT and PD-L1 restores CD226 signaling and antitumor immune response
Role of TIGIT in Cancer Immunity

TIGIT: An emerging inhibitor of antitumor response1,8

Following their discovery of TIGIT, Genentech continues to advance the understanding of TIGIT in cancer immunotherapy research. Targeting TIGIT and PD-L1 is thought to restore multiple steps in the cancer immunity cycle, offering a differentiated mechanism compared to blocking other clinically validated checkpoints, with the goal of improving clinical outcomes.1,2,4,5,9

See how TIGIT works to disrupt critical cancer immunity processes and how dual inhibition with PD-L1 may restore antitumor response.

Recent research suggests that TIGIT and PD-L1 co-blockade may lead to enhanced, long-term tumor control compared to PD-(L)1 inhibition alone, by2,5,7,9-11:

  • Directing differentiation of T cells toward effector cells resistant to exhaustion
  • Promoting expansion of long-lived T cells with improved effector function, resulting in high-quality, and potentially persistent T cell responses
  • Reshaping the tumor microenvironment to facilitate antitumor T cell activity

PD-L1 + TIGIT: Discover what’s next

Genentech's scientific leadership in cancer immunotherapy led to the discovery of TIGIT and the broadest anti-TIGIT clinical development program, across early and metastatic settings, in several types of cancer.

Learn more about what's next in cancer immunotherapy research.

TIGIT clinical trials

Explore ongoing clinical trials investigating complementary inhibition of TIGIT and PD-L1, including the SKYSCRAPER clinical development program

Read More
Contact Genentech

Connect with Genentech to learn more about ongoing TIGIT research

Contact Us

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.

    • Manieri NA, Chiang EY, Grogan JL. TIGIT: a key inhibitor of the cancer immunity cycle. Trends Immunol. 2017;38(1):20-28. doi:10.1016/j.it.2016.10.002

      Manieri NA, Chiang EY, Grogan JL. TIGIT: a key inhibitor of the cancer immunity cycle. Trends Immunol. 2017;38(1):20-28. doi:10.1016/j.it.2016.10.002

    • Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957

      Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957

    • 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. doi:10.1038/s41571-021-00552-7

      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. doi:10.1038/s41571-021-00552-7

    • 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

      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

    • 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

      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

    • 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. doi:10.1016/j.ccell.2014.11.016

      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. doi:10.1016/j.ccell.2014.11.016

    • 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

      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

    • Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint. Clin Exp Immunol. 2020;200(2):108-119. doi:10.1111/cei.13407

      Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint. Clin Exp Immunol. 2020;200(2):108-119. doi:10.1111/cei.13407

    • 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

      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

    • Guan X, Hu R, Choi Y, et al. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature. 2024;627(8004):646-655. doi:10.1038/s41586-024-07121-9

      Guan X, Hu R, Choi Y, et al. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature. 2024;627(8004):646-655. doi:10.1038/s41586-024-07121-9

    • Nutsch K, Banta KL, Wu TD, et al. 579-B TIGIT and PD-L1 co-blockade promotes clonal expansion of non-exhausted anti-tumour CD8+ T cells by facilitating costimulation. J Immunother Cancer. 2023;11(Suppl 2):A1758. doi:10.1136/jitc-2023-SITC2023.0579-B

      Nutsch K, Banta KL, Wu TD, et al. 579-B TIGIT and PD-L1 co-blockade promotes clonal expansion of non-exhausted anti-tumour CD8+ T cells by facilitating costimulation. J Immunother Cancer. 2023;11(Suppl 2):A1758. doi:10.1136/jitc-2023-SITC2023.0579-B