Hypothesizing a similar mechanism to T cells, NK cells would thus become “anergic” if CD137 signaling is absent at the time of NK-aAPC contact, which may be the case when NK cells are within the tumor microenvironment where NK cells contact MHC-I negative tumor cells and may receive IL-2 and/or IL-15 cytokine signaling, without ligation of CD137, which is typically provided by antigen presenting cells. Here, IL2 is linked to neoplasm.