Escaping death: how cancer cells and infected cells resist cell-mediated cytotoxicity
File(s)
Published version
Author(s)
Tuomela, Karoliina
Ambrose, Ashley R
Davis, Daniel M
Type
Journal Article
Abstract
Cytotoxic lymphocytes are critical in our immune defence against cancer and infection. Cytotoxic T lymphocytes and Natural Killer cells can directly lyse malignant or infected cells in at least two ways: granule-mediated cytotoxicity, involving perforin and granzyme B, or death receptor-mediated cytotoxicity, involving the death receptor ligands, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL). In either case, a multi-step pathway is triggered to facilitate lysis, relying on active pro-death processes and signalling within the target cell. Because of this reliance on an active response from the target cell, each mechanism of cell-mediated killing can be manipulated by malignant and infected cells to evade cytolytic death. Here, we review the mechanisms of cell-mediated cytotoxicity and examine how cells may evade these cytolytic processes. This includes resistance to perforin through degradation or reduced pore formation, resistance to granzyme B through inhibition or autophagy, and resistance to death receptors through inhibition of downstream signalling or changes in protein expression. We also consider the importance of tumour necrosis factor (TNF)-induced cytotoxicity and resistance mechanisms against this pathway. Altogether, it is clear that target cells are not passive bystanders to cell-mediated cytotoxicity and resistance mechanisms can significantly constrain immune cell-mediated killing. Understanding these processes of immune evasion may lead to novel ideas for medical intervention.
Date Issued
2022-03-23
Date Acceptance
2022-03-04
Citation
Frontiers in Immunology, 2022, 13
ISSN
1664-3224
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Immunology
Volume
13
Copyright Statement
© 2022 Tuomela, Ambrose and Davis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35401556
Subjects
cancer
cell-mediated cytotoxicity
cytolytic T cells
immune synapse
lymphocytes
natural killer cells
resistance
viral infection
Granzymes
Neoplasms
Perforin
Pore Forming Cytotoxic Proteins
Receptors, Death Domain
Tumor Necrosis Factor-alpha
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
ARTN 867098