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STK11 (LKB1) is a tumor suppressor, and loss-of-function mutations contribute to tumorigenesis. Mutations in the STK11 gene (STK11m) are present in ~ 20% of NSCLCs and are associated with poor response to chemotherapy and immune checkpoint inhibition (ICI) resulting in inferior survival outcomes. STK11m tumors are characterized by high oxidative stress/ROS, EMT, enhanced replication stress tolerance, resistance to DNA damage and a highly immunosuppressive tumor microenvironment with limited activation and expansion of anti-tumor CD8 T-cells. AXL, a member of the TAM family of receptor tyrosine kinases, is activated in response to cellular stress such as ROS and hypoxia. AXL expression and activation is associated with EMT and drug resistance, tumor tolerance towards oxidative stress and apoptosis, as well as an immunosuppressed tumor microenvironment.

We have previously shown that …