TNF and neoplasm: Among the most prominent TNF-α-resistance mechanisms are abnormal DR expression and functioning [50, 51], stoichiometry of the relevant ligand, heterozygous mutations and/or post-translational modifications of DRs and their ligands [50], mitochondrial dysfunctions, deficiency (lower expression or silencing) of key pro-apoptotic proteins/apoptosis pathway effectors (tumor intrinsic and host-related factors), low immunogenic capacity of immune effectors in the TME, and activation of complex pro-survival machinery [39, 51, 52].