Metastasis is the main cause of cancer death, and lung is one of the most common metastatic organs of solid tumors. Cancer cells must overcome many obstacles to gain a foothold in the lungs. Cancer cells newly transplanted into the lungs face many pressures, such as how to escape from immune cells and how to survive in unfamiliar environments by extracting energy. It is generally believed that tumor tissue will change the lung environment and weaken the activity of killer T cells and natural killer (NK) cells before it metastasizes to the lung. The formation of metastatic foci is the main cause of death caused by tumor diseases. Lung is one of the most common metastatic organs of solid tumors. Cancer cells must overcome many obstacles to gain a foothold in the lungs.

It is generally believed that tumor tissue will change the lung environment, destroy the activities of killer T cells and natural killer (NK) cells, and form an immunosuppressive microenvironment before it is transferred to the lung, so that the transferred tumor cells cannot be killed. People know little about the energy intake of cancer cells, so how did cancer cells come to Wan Li to eat in the lungs? Abstract: Lipid storage stimulated by pulmonary interstitial cells was published online in Nature-Immunology by Guang Wenren of JacksonLaboratory and his colleagues.

Li Peishan (Associate Professor, School of Basic Medicine, Shandong University) and Minglu (Associate Professor, Huashan Hospital, Fudan University) are the first authors of this paper. This study shows that neutrophils can be induced to infiltrate into the lungs and store a lot of lipids before tumor cells metastasize. Once tumor cells metastasize to the lungs, these lipid reserves can be used by tumor cells to promote colonization and growth. In this study, the author used a mouse model of breast cancer and found that neutrophils from bone marrow had obvious lipid accumulation from the early stage of metastasis after infiltrating into the lungs. This lipid is not inherent in neutrophils, but is induced by CD 140a+ interstitial cells after reaching the lung.

On the molecular mechanism, pulmonary interstitial cells significantly up-regulated the expression of neutrophil lipid-related genes, including Hilpda, Cidec and G0s2. These up-regulated triglyceride (ATGL) inhibitors will inhibit the enzymatic activity of ATGL, leading to the accumulation of triglycerides in pulmonary neutrophils. Neutrophil-specific knockout of Atgl can enhance intracellular lipid accumulation and significantly promote lung metastasis of breast cancer in vivo. On the contrary, the deletion of Hilpda gene in neutrophils reduces the storage of lipids and obviously inhibits the metastasis and colonization of breast tumors.