Research summary
Human and macaque TIGIT differ in plasmin susceptibility in the tested systems; soluble macaque TIGIT retains CD155 and antibody binding.
Study context
A macaque TIGIT shedding difference
Can a species-specific receptor-processing difference alter how preclinical anti-TIGIT antibody experiments are interpreted?
How it was studied
The authors compared human and macaque TIGIT sequences and plasmin response, examined receptor shedding from rhesus and human PBMCs, and tested binding of the released TIGIT ectodomain to CD155 and tiragolumab. The exact sequence-to-cleavage relationship is discussed in the original paper.
Selected findings
- The paper reports direct plasmin cleavage of macaque TIGIT under tested conditions, unlike the tested human receptor.
- Rhesus PBMCs, but not human PBMCs in the comparison, released soluble TIGIT after plasmin exposure.
This study is a mechanistic comparison relevant to preclinical model choice. It does not establish that macaques are invalid for every TIGIT study or prove a causal explanation of trial outcomes. The article appeared online November 20, 2025 and in the January 2026 issue.
Read the full project analysis → · View figures in the original paper →
Authors
Cite this work
Eric Pirillo, Francis Freenor V, Brice E N Wamba, Sanchita Bhatnagar, Tanmoy Mondal, Jogender Tushir-Singh (2026). An evolutionary T119R substitution in the macaque T-cell immunoreceptor TIGIT enables proteolytic shedding and reveals clinical antibody vulnerabilities. The Journal of biological chemistry, 110962. https://doi.org/10.1016/j.jbc.2025.110962