Liquid and solid tumors differ in their interactions with CAR T cells and it is important to understand the critical factors associated with tumor escape mechanisms. In this webinar, Dr. Rebecca Larson presented her work on “Loss of IFNγR signaling and downstream adhesion confers resistance to CAR T cell cytotoxicity in solid but not liquid tumors” in Nature, and suggests that enhancing binding interactions between T cells may yield improved responses in solid tumors. Learn how cell avidity measurements can improve CAR T cell response in solid tumors by identifying important evasion mechanism.
– The IFNγR1 pathway was identified as an important evasion mechanism of solid tumors, but not liquid tumors, from CAR T cell therapy.
– IFNγR1 signaling leads to upregulation of ICAM-1 and subsequent interactions between ICAM-1 and LFA-1, which stabilize the immune synapse and enhance cell avidity, ultimately leading to increased CAR T cell-mediated cytotoxicity.
– Cell avidity measurements with the z-Movi demonstrated that loss of IFNγR1 in solid tumor cells reduced overall cell avidity, causing reduced CAR T cell killing and resulting in tumor escape.