They showed that IRE1α downregulates Irf4 and Klf4 expression and suppresses M2 polarization, through a mechanism that requires its RNase activity, but presumably not its Xbp1 mRNA splicing activity.23 However, our results showed that XBP1 could upregulate the pro-tumorigenic cytokines expression and reduce the phagocytosis, which could enhance the pro-tumorigenic function of macrophages (M2-like TAMs) in the tumor microenvironment. This evidence concerns the gene ERN1 and neoplasm.