Sensitizing tumor cells to immune-mediated cytotoxicity.
The molecular basis underlying tumor destruction in vivo by specific antitumor CD8+ T cells remains unclear. We propose that the local production of certain tumor necrosis factor (TNF)-family members (death ligands) may be more important for tumor destruction in vivo than previously thought. Also, the apoptotic response of some tumor cells to the TNF-family member TRAIL can be augmented by the proteasome inhibitor bortezomib (Velcade). Thus, bortezomib may sensitize tumor cells to T cell-mediated cytotoxicity and could potentially improve the beneficial effects of immunotherapy.
Shanker
Anil
A
Cancer and Inflammation Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD, USA.
Sayers
Thomas
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D009369:Neoplasms / Q000276:immunology*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D001897:Boronic Acids; D008024:Ligands; D061988:Proteasome Inhibitors; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D000069286:Bortezomib