Human natural killer cells across tissues.

Natural killer cells residing in tissues are distinct compared to those in the bloodstream, and their diversity is likely shaped by the microenvironment of individual tissues.

In tissues, natural killer cells are exposed to an environment with low oxygen levels, a distinct cytokine milieu, and different neighboring cells compared to their circulating counterparts, leading to a unique metabolic and functional profile.

Tissue-resident natural killer cells in most human tissues appear to be only transiently tissue-resident and recirculate via the lymphatic system back to the bloodstream. Lymphatic vessels and lymph nodes contain various natural killer cell populations of distinct origins. Tumor responses of tissue-resident natural killer cells depend on the tissue niche and tumor microenvironment context, with tissue-resident natural killer cells having a more immunoregulatory rather than a direct cytotoxic role during tumorigenesis. sciencenewshighlights ScienceMission https://sciencemission.com/natural-killer-cells

Natural killer (NK) cells are part of the innate immune system and reside in multiple tissues. During steady-state conditions, they contribute to tissue homeostasis, while in disease settings, tissue-resident (tr) NK cells are positioned at the frontline of immune surveillance. Due to their exposure to local microenvironments, NK cells residing outside the bloodstream exhibit phenotypic, transcriptional, functional, and metabolic features that distinguish them from their circulating counterparts. In this review, we outline the defining characteristics of tr NK cells, discuss their recirculation potential, and summarize their functional and metabolic specialization across human tissues. Finally, using cancer as an example, we highlight how tr NK cells are altered in disease and how local tissue environments shape their functional states.