Specific depletion of TIGIThigh CD226- clonally expanded intratumoral Tregs defines safe and effective TIGIT targeting - PubMed
4 hours ago
- #TIGIT
- #Tregs
- #Immunotherapy
- TIGIT blockade clinical programs have been terminated due to inadequate efficacy, necessitating new approaches.
- Multiomics analyses identified TIGIThigh CD226- clonally expanded intratumoral Tregs as a major barrier to effective TIGIT targeting.
- Anti-TIGIT antibodies, especially αTIGIT-IgG1-ADCC, specifically depleted TIGIThigh CD226- Tregs, improving antitumor efficacy.
- Depletion of these Tregs relieved suppression on stem-like CD4+ T cells, promoting their differentiation into Th1 effector cells.
- Th1-derived IFN-γ enhanced CD8+ T cell functionality, correlating with better immunotherapy responses in non-small cell lung cancer patients.
- Targeted elimination of clonally expanded intratumoral Tregs is crucial for maximizing the therapeutic potential of αTIGIT.