Lung-resident natural killer cells control pulmonary tumor growth in mice

Accumulating evidence indicates the importance of natural killer (NK) cells in controlling tumor growth and metastasis. NK cell subsets display diversities in their function and tissue distribution and Mac-1^hi CD27^lo NK cells are the predominant population of lung-resident NK cells. Although the lung is a major organ where primary tumor develops and cancer cells metastasize, there is no clear evidence whether circulating NK cells and/or tissue-resident NK cells control tumor growth in the lung. In the present study, we examined an antitumor function of lung-resident NK cells to control pulmonary tumor growth. In an orthotopic lung tumor model, NK cells controlled pulmonary tumor growth, and mature circulating NK cell subsets were increased in tumor-bearing lungs through a C-X-C motif chemokine receptor 3 (CXCR3)-dependent mechanism. Although such increase in migratory NK cell subsets can be blocked by anti-CXCR3 treatment, there was no difference in pulmonary tumor growth in anti-CXCR3-treated mice compared with control mice. In addition to pulmonary tumor growth, lung-resident NK cells, but not migratory NK cells, play a dominant role in controlling metastatic growth of cancer cells in lung. These results strongly indicate an importance of lung-resident NK cells for controlling pulmonary tumor growth.