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Natural killer (NK) cells were originally identified as lymphocytes capable of killing cancer cells without prior sensitization (1). Further characterization of these cells in both humans and rodent models has expanded their role towards a broad-based immunosurveillance of diseased and healthy peripheral tissues. Among peripheral organs, the lung contains the largest percentage of NK cells. Accordingly, NK cells are implicated in many immunological responses within the lung, including innate effector functions as well as initiation of the adaptive immune response. In this article, we review the characteristics of NK cells, current models of NK maturation and cell activation, migration of NKs to the lung, and effector functions of NKs in cancer and infection in the airways. Specific emphasis is placed on the functional significance of NKs in cancer immunosurveillance. Therapeutic modulation of NK cells appears to be a challenging but promising approach to limit cancer, inflammation, and infection in the lung.

The role of natural killer cells in pulmonary immunosurveillance