The TIGIT ligand overexpressed in many cancers–an emerging checkpoint target for next-generation immunotherapy.
CD155 was originally identified as the poliovirus receptor but has broader functions in cell adhesion and immunity. In cancer, CD155 is overexpressed on tumor cells and myeloid cells, creating an immunosuppressive environment through TIGITLoading... engagement.
The CD155-TIGIT axis represents a druggable checkpoint distinct from PD-1/PD-L1Loading.... Anti-TIGIT antibodies (tiragolumab, vibostolimab, others) are in advanced clinical development, often combined with anti-PD-1.
A Ligand with Two Faces: CD155 on tumor cells can connect with two different receptors on immune cells:
• TIGIT: Suppresses immunity (like a brake)
• CD226: Activates immunity (like an accelerator)
Same ligand, opposite effects depending on which receptor it binds.
As with PD-1/PD-L1Loading..., CD155 expression doesn't guarantee TIGIT engagement. Tumors may express CD155 without functional interaction occurring–or may have high engagement despite modest expression. iFRETLoading... measurement of CD155-TIGIT interaction could identify patients whose tumors actively use this checkpoint.
The FEBS Letters review specifically notes TIGIT as an emerging checkpoint where iFRET could assess functional engagement states.
The Problem: Measuring CD155 expression doesn't tell you which receptor is winning the competition.
The Opportunity: FRET-based measurement could potentially distinguish CD155/TIGIT engagement from CD155/CD226 engagement, revealing the functional balance in each patient's tumor.
Theoretical Application: CD155 serves as ligand for both inhibitory (TIGIT) and activating (CD226) receptors. Expression alone cannot reveal which receptor pathway predominates.
QF-Pro's ability to measure specific protein-protein interactions could potentially distinguish CD155/TIGIT engagement from CD155/CD226 engagement.
Status: Theoretical application pending assay development.
Future potential: CD155 binds both activating and inhibitory receptors. Expression can't tell you which pathway is winning–QF-Pro could measure both interactions to find out.
