Lack of FADD expression confers survival/growth advantages on tumor cells. Absence of FADD protein confers multiple death receptor-mediated apoptosis resistance and allows tumor cells to co-express death receptors and ligands without committing cell death. (A) Lack of FADD contributes to immune escape and resistance to chemotherapy. FADD deficient tumor cells resist death receptor-mediated apoptosis induced by TIL and chemotherapeutic drugs. Anthracyclines increase Fas and FasL expression on tumor cells. Etoposide induces Fas receptor trimerization, leading to Fas-mediated cell death independently of FasL expression. Both drugs enhance TRAIL-R2-mediated apoptosis. (B) Lack of FADD contributes to tumor counter-attack. Lack of FADD expression allows many types of tumor cells to express innocuously functional FasL that can kill TIL. Secretion of TNF-α by AML cells can have cytotoxic effects on TIL. (C) Lack of FADD contributes to tumor growth. In the absence of FADD, Fas signaling leads to a proliferative signal instead of an apoptotic one. Concomitant death receptor and ligand expression, in the absence of FADD, allows autocrine (in red) and paracrine (in orange) proliferation of tumor cells. Activated TIL can contribute to paracrine (in purple) proliferation of FADD-deficient tumor cells.