IFNG and neoplasm: Besides reduced PD-L1 tumor expression, many additional factors could contribute to resistance to anti-PD-1 therapy, including low numbers of exhausted high-avidity T cells, upregulation of other immune checkpoint molecules and receptors such as VISTA and TIM-3, loss of IFN-γ response elements, and macrophage-sequestration of the therapeutic anti-PD1 antibody [83].