Abstract
Simple SummaryCells undergoing stress, viral infection, and malignant transformation express natural killer group 2 member D (NKG2D) ligands on their surface, rendering them susceptible to immunosurveillance. Given this selective pressure exerted on viruses and cancer cells, many viruses and several cancers have evolved means of evading NKG2D recognition. This review highlights the various ways in which stresses, viruses and cancers induce the expression of NKG2D ligands, before comparing the similarities and differences between viral and cancer mechanisms to subsequently prevent recognition by the NKG2D system.The natural killer group 2 member D (NKG2D) receptor and its family of NKG2D ligands (NKG2DLs) are key components in the innate immune system, triggering NK, γδ and CD8+ T cell-mediated immune responses. While surface NKG2DL are rarely found on healthy cells, expression is significantly increased in response to various types of cellular stress, viral infection, and tumour cell transformation. In order to evade immune-mediated cytotoxicity, both pathogenic viruses and cancer cells have evolved various mechanisms of subverting immune defences and preventing NKG2DL expression. Comparisons of the mechanisms employed following virus infection or malignant transformation reveal a pattern of converging evolution at many of the key regulatory steps involved in NKG2DL expression and subsequent immune responses. Exploring ways to target these shared steps in virus- and cancer-mediated immune evasion may provide new mechanistic insights and therapeutic opportunities, for example, using oncolytic virotherapy to re-engage the innate immune system towards cancer cells.
Highlights
Cancer cells have long been defined with a set of characteristics, known as the ‘hallmarks of cancer’, with immune evasion rapidly emerging as a key player in cancer progression [1]
In contrast to T cell activation by clonotypic T cell receptor (TCR) interacting with specific peptides presented in the context of major histocompatibility complex (MHC), natural killer (NK) cells are inhibited by MHC molecules, and are instead activated
Vantourout et al describe a mechanism in which ultraviolet B (UVB) radiation upregulated MICA, MICB and ULBP2 in human epithelial cells via stress-induced epidermal growth factor receptor (EGFR) signalling, rather than due to the DNA damage response (DDR) [36]
Summary
Cancer cells have long been defined with a set of characteristics, known as the ‘hallmarks of cancer’, with immune evasion rapidly emerging as a key player in cancer progression [1]. Viruses share several of these hallmarks with cancer cells to achieve a successful infection, as immune evasion is critically important for viruses
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