Local cues, local killers: human natural killer cells across tissues

Area of Science:

• Immunology
• Cell Biology

Background:

• Natural killer (NK) cells are key components of the innate immune system.
• Tissue-resident (tr) NK cells, distinct from circulating counterparts, play vital roles in tissue homeostasis and immune surveillance.
• Local microenvironments significantly influence the phenotype, function, and metabolism of tr NK cells.

Purpose of the Study:

• To define the characteristics of tissue-resident NK cells.
• To explore the recirculation potential and functional/metabolic specialization of tr NK cells across human tissues.
• To examine how disease, using cancer as a model, alters tr NK cells and their interaction with local tissue environments.

Main Methods:

• Review of existing literature on tissue-resident NK cells.
• Analysis of phenotypic, transcriptional, functional, and metabolic data.
• Case study focusing on NK cell alterations in cancer.

Main Results:

• Tr NK cells exhibit unique features shaped by their tissue of residence.
• Significant differences exist in the functional and metabolic profiles of tr NK cells compared to circulating NK cells.
• Disease states, such as cancer, profoundly alter tr NK cell function and localization.

Conclusions:

• Tr NK cells are specialized immune sentinels with distinct properties.
• Understanding tr NK cell biology is crucial for developing targeted immunotherapies.
• Local tissue environments are critical determinants of tr NK cell activity in health and disease.