Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines

Background: damage-associated molecular patterns (damps) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (dcs). specific microtubule- depolymerizing agents (mdas) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of dcs. methods. in this study,we evaluated the ability of three mdas (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells,activate dcs,and augment t-cell proliferation activity. these mdas were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed dc vaccine. results: the three test phytochemicals considerably increased the expression of damps including hsp70,hsp90 and hmgb1,but had no effect on expression of calreticulin (crt). dc vaccines pulsed with mda-treated tumor cell lysates had a significant effect on tumor growth,showed cytotoxic t-lymphocyte activity against tumors,and increased the survival rate of test mice. in vivo antibody depletion experiments suggested that cd8+ and nk cells,but not cd4+ cells,were the main effector cells responsible for the observed anti-tumor activity. in addition,culture of dcs with gm-csf and il-4 during the pulsing and stimulation period significantly increased the production of il-12 and decreased production of il-10. mdas also induced phenotypic maturation of dcs and augmented cd4+ and cd8+ t-cell proliferation when co-cultured with dcs. conclusions: specific mdas including the clinical drug,colchicine,can induce immunogenic cell death in tumor cells,and dcs pulsed with mda-treated tumor cell lysates (tcls) can generate potent anti-tumor immunity in mice. this approach may warrant future clinical evaluation as a cancer vaccine. © 2011 wen et al; licensee biomed central ltd.