A critical role for Fas-mediated off-target tumor killing in T-cell immunotherapy
R Upadhyay, JA Boiarsky, G Pantsulaia… - Cancer discovery, 2021 - AACR
T cell–based therapies have induced cancer remissions, though most tumors ultimately
progress, reflecting inherent or acquired resistance including antigen escape. Better
understanding of how T cells eliminate tumors will help decipher resistance mechanisms.
We used a CRISPR/Cas9 screen and identified a necessary role for Fas–FasL in antigen-
specific T-cell killing. We also found that Fas–FasL mediated off-target “bystander” killing of
antigen-negative tumor cells. This localized bystander cytotoxicity enhanced clearance of …
progress, reflecting inherent or acquired resistance including antigen escape. Better
understanding of how T cells eliminate tumors will help decipher resistance mechanisms.
We used a CRISPR/Cas9 screen and identified a necessary role for Fas–FasL in antigen-
specific T-cell killing. We also found that Fas–FasL mediated off-target “bystander” killing of
antigen-negative tumor cells. This localized bystander cytotoxicity enhanced clearance of …