| First Author | Ziegler PK | Year | 2018 |
| Journal | Cell | Volume | 174 |
| Issue | 1 | Pages | 88-101.e16 |
| PubMed ID | 29909986 | Mgi Jnum | J:264154 |
| Mgi Id | MGI:6192957 | Doi | 10.1016/j.cell.2018.05.028 |
| Citation | Ziegler PK, et al. (2018) Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell 174(1):88-101.e16 |
| abstractText | In colorectal cancer patients, a high density of cytotoxic CD8(+) T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/beta-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8(+) T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8(+) T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer. |
