This proteolytic inactivation of IFNAR1 is mediated by either protein kinase D2 in response to IFN1 itself55 or by p38 protein kinase in response to the non-ligand stimuli that are present in the tumor microenvironment including pro-inflammatory cytokines, tumor-derived vesicles, and the deficit of oxygen/nutrients leading to the integrated stress response33,38,39. This evidence concerns the gene PRKD2 and neoplasm.