Effect of mechanical cues on T cell killing of cancer cells

Abstract Cancer immunotherapies have focused on strategies to strengthen immune cell activation and effector function. These treatment enhance the function of cells, particularly cytotoxic T cells (CTL), driving tumor eradication. Methods improve killing mechanisms CTLs are not well studied largely assessing/strengthening antigenic responses cells. We hypothesize that mechanical landscape CTL-tumor interactions can also drastically impact CTL cytotoxicity. By altering physical context for recognition tumors, we measured cytotoxicity changes subsequently used these in capacities train generate a quantitative parametrization killing. utilize cytokine expression kill shape inflammatory milieu. Taking advantage robotic platform enables automatic collection cytokines, assembled datasets attacks grown substrates with varying stiffness levels. The levels were altered using polyacrylamide (PAA) gels ranged from 0.2kPa approximately 113 kPa. Preliminary results two different models (i.e., mouse human TCR-transgenic cells) suggest there exists an optimal value maximal response by biophysical cues addition molecular (antigen) properly elicit response—modeling fine-tuning be novel effective approach improving cancer immunotherapies.