TNF and melanoma: 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.