ESCRT-mediated membrane repair protects tumor-derived cells against T cell attack
- Author(s)
- Ritter, AT; Shtengel, G; Xu, CS; Weigel, A; Hoffman, DP; Freeman, M; Iyer, N; Alivodej, N; Ackerman, D; Voskoboinik, I; Trapani, J; Hess, HF; Mellman, I;
- Details
- Publication Year 2022-04-22,Volume 376,Issue #6591,Page 377-382
- Journal Title
- Science
- Publication Type
- Research article
- Abstract
- Cytotoxic T lymphocytes (CTLs) and natural killer cells kill virus-infected and tumor cells through the polarized release of perforin and granzymes. Perforin is a pore-forming toxin that creates a lesion in the plasma membrane of the target cell through which granzymes enter the cytosol and initiate apoptosis. Endosomal sorting complexes required for transport (ESCRT) proteins are involved in the repair of small membrane wounds. We found that ESCRT proteins were precisely recruited in target cells to sites of CTL engagement immediately after perforin release. Inhibition of ESCRT machinery in cancer-derived cells enhanced their susceptibility to CTL-mediated killing. Thus, repair of perforin pores by ESCRT machinery limits granzyme entry into the cytosol, potentially enabling target cells to resist cytolytic attack.
- Keywords
- *Endosomal Sorting Complexes Required for Transport/genetics/metabolism; Granzymes/metabolism; *Membrane Glycoproteins/metabolism; Perforin/genetics/metabolism; Pore Forming Cytotoxic Proteins/genetics/metabolism; T-Lymphocytes, Cytotoxic/metabolism
- Department(s)
- Laboratory Research
- PubMed ID
- 35446649
- Publisher's Version
- https://doi.org/10.1126/science.abl3855
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-03-07 05:57:21
Last Modified: 2025-03-07 06:00:21