The immune-modulating therapeutic, IRX-2, is a cytokine-based primary cell-derived biologic consisting of multiple well-defined active cytokine components, including interleukin (IL)-1β, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNFα), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) (Freeman and others 2011), and has recently been used in early stage clinical trials as an immune-enhancing agent for HNSCC patients (Freeman and others 2011; Wolf and others 2011; Berinstein and others 2012; Whiteside and others 2012). Here, TNF is linked to head and neck squamous cell carcinoma.