Year: 2022
Type: review
Abstract: Immune effector cells, including cytotoxic T cells (CTLs), induce apoptosis and eliminate target cells by direct cell-cell contacts. In vivo, CTLs fail to efficiently kill solid tumor cells by individual contacts but rely upon multihit interactions by many CTLs (swarming). Recent evidence has indicated that multihit interactions by CTLs induce a series of sublethal damage events in target cells, including perforin-mediated membrane damage, induction of reactive oxygen species (ROS), nuclear envelope rupture, and DNA damage. Individual damage can be repaired, but when induced in rapid sequence, sublethal damage can accumulate and induce target cell death. Here, we summarize the sublethal damage and additive cytotoxicity concepts for CTL-induced and other cell stresses and discuss the implications for improving immunotherapy and multitargeted anticancer therapies.
Source: Trends in cancer
Authors: Bettina Weigelin, Peter Friedl
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $6,700
Funders: Fritz-Bender-Stiftung, European Commission, Deutsche Forschungsgemeinschaft, Eberhard Karls Universität Tübingen, Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg, National Institutes of Health, Horizon 2020 Framework Programme, European Research Council, National Cancer Institute, H2020 European Research Council
Awards: G2532469498, G2853181762, G3105035837, G3153959770, Center on the Physics of Cancer Metabolism, Training European Experts in Inflammation: from the molecular players to animal models and the bedside, G4085951184, G4937468798, G5476487584, G6260673471, G7980353291, G8858395165, G9000178996, Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth, EXC 2180: Individualisierung von Tumortherapien durch molekulare Bildgebung und funktionelle Identifizierung therapeutischer Zielstrukturen (iFIT)
OpenAlex ID: W4291001388