ISG15 and neoplasm: Previous work demonstrated that extracellular free ISG15 can activate natural killer (NK) cells (18), induce non-major histocompatibility complex-restricted cytolysis of tumor cell targets by NK-derived lymphokine-activated killer (LAK) cells [18], stimulate IFNγ production from T cells [18], induce dendritic cell maturation [19], and neutrophil recruitment [19].