Killer instincts: natural killer cells as multifactorial cancer immunotherapy

Abstract

Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.

El sistema inmune y su interminable batalla contra las células tumorales: reconocimiento, eliminación y evasión de la respuesta inmune

“…Existe una gran diversidad de receptores de activación, dentro de los más estudiados se encuentran los miembros de la familia de los NCRs (receptores naturales de citotoxicidad, como NKp30, NKp44, y NKp46), y los miembros de la familia NKG2 (NKG2C y NKG2D). Los principales receptores de ISSN 2007-3380 inhibición incluyen a los miembros de la familia de los KIR (receptores tipo inmunoglobulina de las células NK) y NKG2A (miembro de la familia NKG2) (Nersesian et al, 2023). La expresión y coexpresión de los diversos receptores está asociada con poblaciones de células NK con diferente estado de maduración y función.…”

Changes in subset distribution and impaired function of circulating natural killer cells in patients with colorectal cancer

“…Previous studies have explored the correlation between NK cells and the progression and metastasis of different types of malignant tumors 17 , 18 . Exploratory strategies for cancer immunotherapy using NK cells have been proposed 19 , 20 . However, research on the correlation between NK cells and CRC is limited.…”