IL34 is expressed in primary lung adenocarcinoma tissues and correlates with poor prognosis in cancer patients. IL34, a cytokine that acts as a second ligand for CSF1R, was found to be induced and controlled by chronic activation of NF-κB in chemoresistant lung cancer cells. In vitro and in vivo experiments unveiled a dual role for IL34 in cancer chemoresistance. IL34 was found to enhance local immunosuppression by tumor-associated macrophages and also provides cancer cells with a critical survival signal to overcome chemotherapeutic conditions. For details, see article by Baghdadi and colleagues on page 6030.