Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor

This episode explores groundbreaking research that uncovers a novel link between the mechanical properties of the tumor microenvironment and CD8+ T cell exhaustion, a major hurdle for effective cancer immunotherapy.

Key Findings:

• Stiffer tumor regions, rich in collagen, harbor a higher proportion of exhausted CD8+ T cells.
• Mechanical stress, mimicked by culturing T cells on stiff matrices or using a cell stretching device, exacerbates T cell exhaustion.
• The mechanosensitive ion channel Piezo1 is essential for this process, as Piezo1-deficient T cells show reduced exhaustion in response to mechanical stress.
• The transcription factor Osr2 emerges as a key downstream mediator of this pathway, specifically induced in activated T cells under mechanical stress.
• Osr2 expression is directl ...