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The presence of apoptosis-inducing membraneous microvesicles (MV) in sera of patients with cancer has been linked to death of immune cells. We and others have shown that MV-mediated T-cell apoptosis involves the Fas/FasL pathway. However, among 27 MV initially isolated from sera of patients with head and neck cancer (HNC), 7 did not express FasL in Western blots, yet all induced DNA fragmentation in activated T lymphocytes and in Fas-resistant Jurkat cells. In Western blots, these MV were found to contain various levels of HLA class I molecules (HLA-I), and their biologic activity was blocked by anti-HLA-I mAbs, TP25.99 and W6/32. MV obtained from other HNC patients’ sera and co-incubated with activated T cells induced DNA fragmentation and caspase 3 cleavage, which were completely blocked by anti-Fas and anti-HLA-I Abs but only partially (e.g., 40-50%) by TP25.99 Ab alone. Thus, MV-associated FasL and/or HLA-I antigens mediated apoptosis of T cells. We have reported that CD8+ effector T cells are especially sensitive to MV-mediated apoptosis in patients with cancer. Pre-incubation of activated T cells with Abs to the CD8 molecule inhibited MV-induced apoptosis, while Abs to TcR did not. This finding implicates the CD8 complex signaling in MV-mediated apoptosis, possibly through mechanisms involving an interaction of MV-associated HLA-I antigens with CD8. We consider this molecular mechanism to be particularly relevant to tumor escape from immune cells in patients with cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]