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.
Original language | English (US) |
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Pages (from-to) | 980-987 |
Number of pages | 8 |
Journal | Trends in Cancer |
Volume | 8 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2022 |
Keywords
- apoptosis
- cell damage
- cell stress
- cytotoxic T cells
- immunotherapy
ASJC Scopus subject areas
- Oncology
- Cancer Research