KDM1B is an important regulator of cytokine signaling in the tumor immune microenvironment and response to immune checkpoint therapy (ChIP-seq)

Tumor microenvironment (TME) plays an important role in immune evasion and resistance to immune checkpoint therapy. Here, by using genetic, epigenetic, tumor biology and immunology approaches, we unraveled a key function of KDM1B in TME. KDM1B is important for maintaining several pro-oncogenic cytokine/chemokine signaling pathways. In vivo in resistant and inflammatory breast cancer models, ablation of KDM1B in tumor cells results in increased T cell activity and significantly improved response to anti-PD-1/anti-CTLA-4 therapy. Thus, this study identifies KDM1B as a key regulator of tumor immune microenvironment and offered the mechanistical basis for using KDM1B inhibitors in combinatory therapy to overcome resistance to immune checkpoint blockade. Use ChIP-seq to characterize the genome-wide KDM1B distritution in the genome.