TNF and neoplasm: Additionally, tumor-specific cytotoxic T lymphocytes (CTL) activated by biNV-IL-15 could produce proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which mediate phenotypic polarization of M2-type tumor-associated macrophages (TAM) to antitumoral M1-type TAMs, in turn, impede the immunosuppressive effects of regulatory T cells (Treg) within the tumor microenvironment (TME) (Fig. 1b)33.