0000000000769173
AUTHOR
Claudio Procaccini
PD‐1‐induced T cell exhaustion is controlled by a Drp1‐dependent mechanism
Programmed cell death‐1 (PD‐1) signaling downregulates the T‐cell response, promoting an exhausted state in tumor‐infiltrating T cells, through mostly unveiled molecular mechanisms. Dynamin‐related protein‐1 (Drp1)‐dependent mitochondrial fission plays a crucial role in sustaining T‐cell motility, proliferation, survival, and glycolytic engagement. Interestingly, such processes are exactly those inhibited by PD‐1 in tumor‐infiltrating T cells. Here, we show that PD‐1pos CD8+ T cells infiltrating an MC38 (murine adenocarcinoma)‐derived murine tumor mass have a downregulated Drp1 activity and more elongated mitochondria compared with PD‐1neg counterparts. Also, PD‐1pos lymphocytic elements in…
PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism
AbstractPD-1 signalling downregulates the T cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Drp1-dependent mitochondrial fission plays a crucial role to sustain T cell motility, proliferation, survival and glycolytic engagement and, interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here we show that the signature of PD-1pos CD8+ T cells infiltrating MC38-derived murine tumor mass is having downregulated Drp1 activity and more fused mitochondria, compared to PD-1neg counterparts. Also, PD-1pos lymphocytic elements infiltrating human colon cancer rarely express active Drp1. …