Update in TIGIT Immune-Checkpoint Role in Cancer

Abstract

The in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT.

Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives

“…Furthermore, TLR7/8 agonists may be a potential adjuvant for future anti-angiogenic therapy. Recently, clinical research focus has expanded from the combination of different TLR target agonists to selective single TLR agonist and in selective combination with other immune target therapy regimens, such as PD-1/PD-L1, CTLA-4, TIGIT and LAG3 [179][180][181][182]. So far, there has been no breakthrough in the research of innate immune drugs regarding TLRs, and the selectivity and effectiveness are not clear yet.…”

Targeting TIGIT in NSCLC—Is There Light on the Horizon?

“…From 2021 onwards different TIGIT family receptors are currently evaluated in over 25 clinical trials (phase I-III) [11], however, a lot of preclinical and clinical research is ongoing at different research sites which will help to identify novel immune checkpoint targets with improved activity against malignancies across all histologies.…”

“…These receptors include TIGIT, CD226 (formerly DNA X-associated molecule 1), CD96 (TACTILE: T cell activation, increased late expression), and CD112R (also known as PVRIG, PVR-related Ig domain). These molecules interfere with PVR (CD155), nectin-1 (CD111), nectin-2 (CD112), nectin-3 (CD113), and/or nectin-4 (known as PVRL4) [11].…”

Immune checkpoint inhibitors in cervical cancer: Current status and research progress

“…LAG3 is an inhibitory receptor that is overexpressed on T cells in many types of cancer and can negatively regulate T cell function ( 21 ). GITR is a transmembrane protein expressed on Treg, CD4+ and CD8+ T cells, and B cells, inducing responder T cell resistance to Treg-mediated suppression ( 22 ).TIM3, and TIGHT are two other inhibitory receptors that are expressed in multiple immune cells and can also regulate the immune response through complex mechanisms ( 23 , 24 ). TIM3 can mediate inhibition of T cell proliferation, reduction in cytokine production via TIM3/Gal9 signaling pathway ( 25 ).…”

“…TIM3 can mediate inhibition of T cell proliferation, reduction in cytokine production via TIM3/Gal9 signaling pathway ( 25 ). TIGHT binds to CD155, which expressed on multiple cell types, and induces a tolerogenic phenotype in T cells ( 24 ).…”