Research summary
A human FasL P153S substitution is linked to plasmin cleavage and reduced FasL function in specific experimental tumor settings.
Study context
Human FasL, evolution and plasmin cleavage
Why can Fas ligand displayed by activated T cells lose cell-death function in a plasmin-rich tumor environment?
How it was studied
The authors compared FasL sequences among primates, tested recombinant and cell-associated ligand cleavage by plasmin, examined activated lymphocytes, and used ovarian tumor model systems to test functional consequences. The paper reports interventions that block plasmin access to FasL or inhibit plasmin activity.
Selected findings
- The authors identify human FasL P153S as a change associated with plasmin susceptibility compared with tested nonhuman-primate FasL sequences.
- In studied cellular settings, plasmin exposure reduces membrane FasL availability and FasL-mediated tumor-cell killing.
This is preclinical mechanistic research. It does not prove that P153S determines individual cancer risk or that plasmin inhibition improves patient outcomes. The tumor settings and intervention conditions were specific to the paper.
Read the full project analysis → · View publication figures →
Authors
Cite this work
Brice E N Wamba, Tanmoy Mondal, Francis Freenor V, Mehr Shaheed, Oliver Pang, Daniel Bedinger, Patrick Legembre, Laurent Devel, Sanchita Bhatnagar, Gary Scott Leiserowitz, Jogender Tushir-Singh (2025). Evolutionary regulation of human Fas ligand (CD95L) by plasmin in solid cancer immunotherapy. Nature communications, 5748. https://doi.org/10.1038/s41467-025-60990-0