TNF and cancer: Unfortunately, cancer cells developed a number of defense mechanisms e.g., the absence of NK cells, macrophages or T lymphocytes in the tumor stroma, lack of pro-inflammatory cytokines in the tumor microenvironment (IL-6, IL-2, IL-12, TNF-alpha), production of immunosuppressive compounds (TGF-beta, indoleamine dioxygenase or neutralization of immune cells through direct immune checkpoints interactions (CD80/CD86 with CTLA-4 and PD-L1 with PD-1) that eventually make treatment ineffective.