Several MEL genes (IRF4, IL16, IL6R) that are known to be associated with an anti-tumor milieu (e.g. lymphocyte activation, chemotaxis, and differentiation)73 appear actively suppressed in MES cells through mechanisms such as miR-125b-5p targeting and DNA methylation, reinforcing a potentially immunotherapy-resistant microenvironment. The gene discussed is IRF4; the disease is neoplasm.