Critical and distinct roles of cell type-specific NF-scB2 in lung cancer

Different from the well-studied canonical NF-scB member RelA, the role of the noncanonical NF-scB member NF-scB2 in solid tumors, and lung cancer in particular, is poorly understood. Here we report that in contrast to the tumor-promoting role of RelA, NF-scB2 intrinsic to lung epithelial and tumor cells had no marked effect on lung tumorigenesis and progression. On the other hand, NF-scB2 limited dendritic cell number and activation in the lung but protected lung macrophages and drove them to promote lung cancer through controlling activation of noncanonical and canonical NF-scB, respectively. NF-scB2 was also required for B cell maintenance and T cell activation. The antitumor activity of lymphocyte NF-scB2 was dominated by the protumor function of myeloid NF-scB2; thus, NF-scB2 has an overall tumor-promoting activity. These studies reveal a cell type-dependent role for NF-scB2 in lung cancer and help understand the complexity of NF-scB action and lung cancer pathogenesis for better design of NF-scB-targeted therapy against this deadliest cancer.