Bortezomib sensitizes RENCA tumor cells to NK-cell perforin granzyme-mediated apoptosis and to recombinant TRAIL (rTRAIL), but not FasL-mediated apoptosis. RENCA tumor cells were treated with 20 nM bortezomib for 18 hours and analyzed for susceptibility to (A) wild-type BALB/c NK-cell lysis of RENCA tumors in the presence or absence of CMA (20 nM), neutralizing antibodies to TRAIL (N2B2; 10 μg/mL), or FasL (MFL3; 10 μg/mL). (B) Wild-type (wt) or perforin deficient (pfp−/−) BALB/c NK-cell lysis of RENCA tumors in a 4-hour ⁵¹Cr release assay. (C) RENCA tumor cells were treated with 20 nM bortezomib for 18 hours and analyzed for susceptibility to lysis by (left panel) anti-Fas antibody (Jo2; 10 μg/mL) or rTRAIL (1 μg/mL) in an 18-hour ⁵¹Cr release assay, or to (right panel) syngeneic NK cells in the presence of neutralizing antibodies to NKG2D (2 μg/mL). Error bars depict SD.