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TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.
Haozhe Cui1, Mawieh Hamad2, Eyad Elkord3,4
1Department of Biosciences and Bioinformatics & Suzhou Municipal Key Lab of Biomedical Sciences and Translational Immunology, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu, China.
The TIGIT immune checkpoint inhibits T and NK cell activity. Novel combination therapies and alternative approaches are being explored due to limitations with anti-TIGIT antibody monotherapy in clinical trials.
Area of Science:
- Immunology
- Cancer Biology
- Drug Development
Background:
- TIGIT (T cell immunoreceptor with Ig and ITIM domains) is an immune checkpoint protein.
- It suppresses T and NK cell cytotoxic functions through various mechanisms.
- TIGIT belongs to the PVR-like protein family and interacts with CD155.
Purpose of the Study:
- To review the mechanisms of TIGIT-mediated immune suppression.
- To discuss emerging immunotherapeutic strategies targeting TIGIT.
- To provide an overview of current clinical trials and future directions for TIGIT-based therapies.
Main Methods:
- Literature review of TIGIT function and therapeutic strategies.
- Analysis of preclinical and clinical trial data for anti-TIGIT therapies.
- Discussion of alternative approaches beyond monoclonal antibodies.
Main Results:
- TIGIT inhibits anti-tumor immunity by suppressing T and NK cell activity.
- Anti-TIGIT monoclonal antibody monotherapy has shown limited clinical success.
- Combination therapies and alternative strategies like small molecule inhibitors and CAR-T cells show promise.
Conclusions:
- Understanding TIGIT's complex inhibitory mechanisms is crucial.
- Combinatorial immunotherapies targeting TIGIT offer a promising avenue for cancer treatment.
- Further research into alternative TIGIT-targeting strategies is warranted to overcome current limitations.

