Consistent with this hypothesis, simultaneous inhibition of PDL1-PD1 interactions and induction of trained immunity has been shown to elicit durable anti-tumor responses that significantly reduce tumor growth in murine melanoma models.72 On the other hand, macrophages expressing ICOSL and CD206 are associated with anti-inflammatory responses and have been reported to produce lower levels of IL-6 and TNF following LPS stimulation.73,74 The observed downregulation of these inhibitory molecules in trained macrophages is consistent with an enhanced stimulatory immune phenotype. This evidence concerns the gene ICOSLG and melanoma.