Adaptive natural killer cell expression in response to cytomegalovirus infection in blood and solid cancer

Abstract

Natural Killer (NK) cells are conventionally thought to be an indefinite part of innate immunity. However, in a specific subset of NK cells, recent data signify an extension of their “duties” in immune surveillance and response, having characteristics of adaptive immunity, in terms of persistence and cytotoxicity. These cells are known as the adaptive or memory-like NK cells, where human cytomegalovirus (HCMV) infection has been shown to drive the expansion of adaptive NKG2C+ NK cells. HCMV is a ubiquitous pathogen whose prevalence differs worldwide with respect to the socioeconomic status of countries. The adaptive NK cell subpopulation is often characterized by the upregulated expression of NKG2C, CD16, and CD2, and restricted expression of NKG2A, FCεRγ and killer immunoglobulin-like receptors (KIR), although these phenotypes may differ in different disease groups. The reconfiguration of these receptor distributions has been linked to epigenetic factors. Hence, this review attempts to appraise literature reporting markers associated with adaptive or memory-like NK cells post-HCMV infection, in relation to solid cancers and hematological malignancies. Adaptive NK cells, isolated and subjected to ex vivo modifications, have the potential to enhance anti-tumor response which can be a promising strategy for adoptive immunotherapy.