Figure 2.

NK cell hypofunction and exhaustion are modulated by key components of the lung microenvironment and lung tumor microenvironment. PGE2 and TGF-β secreted by lung epithelial cells, AMs, and fibroblasts in the lung microenvironment modulate the hypofunction of lung NK cells in homeostasis. When tumors grow in the lungs, more PGE2 and TGF-β are secreted by multiple cell types, including tumor cells, MDSCs, TAMs, CAFs, and Tregs. The physical and chemical environment changes to hypoxia, lower glucose, and low pH. All these factors promote NK cell exhaustion in the lung tumor microenvironment. Created with BioRender.com.