Abstract #1871: Autophagy regulation of HMGB1 release from dying tumor cells

The characteristics of tumor cell killing by an anti-cancer agent can determine the long-term effectiveness of the treatment. For example, if dying tumor cells release the immune modulator HMGB1 after treatment with anti-cancer drugs, they can activate a tumor-specific immune response that boosts the effectiveness of the initial treatment. We recently found that in response to tumor cell killing by an Epidermal Growth Factor-Receptor-targeted toxin, the induction of autophagy controls whether or not HMGB1 is released from dying tumor cells. Here we have examined the mechanism by which autophagy controls HMGB1 release in other tumor cells and the role of this mechanism in regulating the ability of other anti-cancer agents treat tumor cells. We found that as with the EGFR-targeted toxin, autophagy regulates HMGB1 after treatment with other anti-cancer agents including doxorubicin. These data identify a new function for autophagy during tumor cell killing by anti-cancer agents and open up the possibility of manipulating autophagy during cancer treatment as a way to influence the immunogenicity of the dying tumor cells.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1871.