TNF and head and neck squamous cell carcinoma: Strategies for relieving immunosuppression in HNSCC to restore anti-tumor immune functions, include the neoadjuvant IRX-2, derived from stimulating human PBMCs with phytohemagglutinin (326). IRX-2 contains a cocktail of cytokines including IL-2, IL-1β IL-6, IL-8, TNFα, GM-CSF, and IFNγ (Table 1). In vitro studies have shown that IRX-2, enhances DC maturation, T cell activation, and NK cell stimulation, to overcome tumor-mediated immunosuppression by activating the tumor environment (326).