CYCS and neoplasm: TDEs are likely to be at least partially responsible for spontaneous apoptosis of CD8+ T‐cells in vivo through their expression of FASL (Figure 2).149 The apoptotic effect of TDEs from oral and ovarian cancers has been attributed to caspase‐3 cleavage, cytochrome C release, loss of mitochondrial membrane potential and signaling defects in CD3‐ζ chain and JAK3 in T‐cells.147, 150 Observation of FasL+ TDEs in the circulation as well as at tumor sites indicate that the immunoinhibitory influence of tumors might extend far beyond the tumor sites and may be a systemic effect.