Anti-tumor and pro-tumor interactions of human NK cells in cancer

摘要: While natural killer (NK) cells have been classically understood as innate cytotoxic effector cells, a new paradigm has emerged involving NK key immunomodulators in the development of both and adaptive immune responses. In particular, can critically shape character anti-cancer immunity through their engagement with dendritic (DCs). Thus, understanding interactions DCs, well other cell types human tumor environment, is essential to endogenous anti-tumor responses developing effective cancer immunotherapies. In this work, we show that perform distinct 'effector' 'helper' activities, which be uniquely driven by cytokine activation. IL-2-activated efficiently kill immature mature IL-18-activated instead potentiate DC activation enhancement DC-induced type-1 immunity. These helper further recruit facilitating productive NK-DC interaction, subsequently collaborate DCs promoting chemokine environments conducive naive T priming lymph nodes infiltration into peripheral sites. However, our studies also indicate that, addition desirable type-1-polarizing such may undesirable pro-tumor effects IFNg- TNFa-dependent hyper-activation myeloid-derived suppressor (MDSCs), critical population present most cancers play major role tumor-associated suppression potential modulation Th17 Using MDSCs isolated directly from malignant ascites patients late-stage ovarian cancer, implicate autocrine COX2/PGE2 feedback cell-mediated MDSC hyper-activation, highlighting possibility for therapeutic axis inhibition reversing up-regulation activity, while preserving or enhancing DCs. Overall, these help better understand between immunity, identify targets manipulation anti- activities improvement therapy.