TIGIT: Brake or Springboard Against Cancer?

#Oncology  #Immunotherapy  #TIGIT  #Cancer  #TherapeuticCombination  #NKCell #TLymphocyte  #PredictiveBiomarker

Immunotherapy has revolutionized cancer treatment by leveraging the immune system to fight tumor cells. However, despite its successes, it often faces resistance that limits its effectiveness, particularly in advanced cancers. Among the mechanisms of tumor immune evasion, the role of TIGIT (T-cell immunoreceptor with Ig and ITIM domains) has garnered increasing attention.

TIGIT is an inhibitory molecule expressed on T lymphocytes and NK cells, two essential players in the anti-tumor immune response. TIGIT interacts with ligands such as CD155, which are widely expressed on tumor cells and their microenvironment. This interaction inhibits T cell activation and reduces NK cells' ability to destroy cancer cells. As a result, tumors evade immune surveillance, promoting their growth and spread. TIGIT acts as an immunological brake, interacting with ligands like CD155 to suppress immune cell activation. Its increased expression in the tumor environment fosters immunosuppression and tumor progression.

TIGIT is an inhibitory molecule expressed on T lymphocytes and NK cells, two pillars of the anti-tumor immune response. By binding to its ligand CD155, which is abundantly present on tumor cells and their microenvironment, TIGIT blocks T cell activation and limits NK cell cytotoxicity. This immunosuppressive mechanism allows tumors to escape immune surveillance, promoting their proliferation and dissemination. The increased expression of TIGIT in the tumor environment acts as a powerful immunological brake, reinforcing tumor progression.

This pathway has emerged as a key therapeutic target in onco-immunology. By targeting TIGIT, it becomes possible to reactivate these immune cells and restore their ability to recognize and eliminate cancer cells, offering a promising new approach to overcoming current immunotherapy limitations.

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TIGIT: The New Key to Boosting Immunotherapy?

To understand the role of TIGIT and its ligand in tumor immune evasion, murine models and human tumor samples were selected and analyzed. The selection and study of phase I and II clinical trials enabled the characterization of the efficacy of anti-TIGIT monoclonal antibodies (e.g., tiragolumab and vibostolimab), either alone or in combination with PD-1/PD-L1 inhibitors. The effectiveness of these therapies was assessed by evaluating the following outcome variables: objective response rate, overall survival, and progression-free survival. At the same time, toxicity profiles were analyzed to measure the risks associated with these therapies. Finally, the study explored the effects of therapeutic combinations aimed at optimizing immune responses and overcoming tumor resistance.

These studies demonstrate that TIGIT blockade effectively restores the antitumor activity of T lymphocytes and NK cells, enhancing their ability to detect and destroy tumor cells. In animal models, this approach significantly reduces tumor growth. Clinically, trials combining anti-TIGIT antibodies, such as tiragolumab, with immune checkpoint inhibitors like PD-1/PD-L1 blockers have shown encouraging results. These findings are particularly significant in non-small cell lung cancer (NSCLC) and melanoma. Such combination therapies improve overall survival and progression-free survival while strengthening immune responses. Although the data remain preliminary, they suggest significant potential for patients with advanced or resistant cancers.

TIGIT: A New Hope for Immunotherapy

Cancer remains one of the leading causes of mortality worldwide. Despite advances in immunotherapy, many patients develop resistance to existing treatments. Identifying new immune targets is therefore essential to improving the management of advanced and resistant cancers.

This study explored the role of TIGIT in tumor immune evasion and evaluated the efficacy of anti-TIGIT therapies, alone or in combination with PD-1/PD-L1 inhibitors. The objective was to analyze their impact on immune cell activation and patient survival while identifying the most promising approaches to optimize their effectiveness.

The results show that TIGIT blockade can enhance antitumor immunity and improve treatment responses. Clinical trials combining anti-TIGIT antibodies with other immunotherapies, particularly PD-1/PD-L1 inhibitors, suggest a potential benefit in terms of survival and tumor control. However, these therapies are not effective in all patients, highlighting the need for better patient selection.

Future research should refine therapeutic combinations and identify predictive biomarkers to better target patients. Combining anti-TIGIT therapies with other immune strategies could offer an effective alternative for resistant cancers and promote more personalized immunotherapy. Additionally, the long-term safety and tolerance of these treatments must still be evaluated on a larger scale to ensure their safety.  

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