Relevantly, using Ern1 (the gene coding for IRE1α) or Xbp1 macrophage conditional knockout mice, we determined that IRE1α-XBP1 axis deficiency in macrophages not only attenuates the development of the pro-inflammatory/immune suppressive phenotype in vivo but also reduces PD-L1 expression, significantly slowing growth of B16.F10 melanoma cells in vivo, and improving survival of Ern1 (-/-) over Ern1 fl/fl control mice (74). The gene discussed is ERN1; the disease is melanoma.