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     Black line: Control Antigen (100 ng);Purple line: Antigen (10ng); Blue line: Antigen (50 ng); Red line:Antigen (100 ng)    

  
  

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     Flow cytometric analysis of K562 cells using TIGIT mouse mAb (green) and negative control (red).    

  
  

TIGIT (T cell immunoreceptor with Ig and ITIM domains) is an inhibitory immune checkpoint receptor expressed on T cells and natural killer (NK) cells. It belongs to the CD28 family and binds to ligands such as CD155 (PVR), CD112 (PVRL2), and CD113 (PVRL3), which are often overexpressed on tumor cells and antigen-presenting cells. TIGIT suppresses immune activation by competing with the co-stimulatory receptor CD226 for ligand binding, thereby dampening T/NK cell-mediated antitumor responses. Its signaling involves recruitment of phosphatases like SHIP1 to inhibit downstream pathways, reducing cytokine production and cytotoxic activity.

Therapeutic targeting of TIGIT aims to reverse this immunosuppression. Preclinical studies show that anti-TIGIT antibodies, either alone or in combination with PD-1/PD-L1 inhibitors, enhance antitumor immunity by restoring T/NK cell function. This synergy arises from TIGIT and PD-1 operating through non-redundant pathways. Clinical trials are evaluating anti-TIGIT agents (e.g., tiragolumab, vibostolimab) in cancers like NSCLC, with mixed phase III results highlighting the need for biomarker-driven patient selection. Challenges include understanding resistance mechanisms and optimizing combination strategies. Despite setbacks, TIGIT remains a promising target in immuno-oncology due to its role in regulating adaptive and innate antitumor immunity.