Abstract
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.