Consequently, the transition from a “cold” to a “hot” tumor immune microenvironment occurs, accompanied by changes in the secretion levels of immunostimulatory and immunosuppressive factors (up-regulation of IFN-γ, TNF-α, and IL-12; down-regulation of IL-4, IL-6, and IL-10), as well as the depletion of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumor-associated macrophages 2 (TAM2) (21). Here, TNF is linked to neoplasm.