TY - JOUR
T1 - Strange attractors
T2 - DAMPs and autophagy link tumor cell death and immunity
AU - Hou, W.
AU - Zhang, Q.
AU - Yan, Z.
AU - Chen, R.
AU - Zeh, H. J.
AU - Kang, R.
AU - Lotze, M. T.
AU - Tang, D.
N1 - Funding Information:
Acknowledgements. We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by the National Institutes of Health (NIH) (R01CA160417 to DT) and the American Association for Cancer Research (AACR) (13-20-25-TANG to DT). We apologize to the researchers who are not referenced because of space limitations.
PY - 2013/12
Y1 - 2013/12
N2 - Resistance to 'apoptotic' cell death is one of the major hallmarks of cancer, contributing to tumor development and therapeutic resistance. Damage-associated molecular patterns (DAMPs) are molecules released or exposed by dead, dying, injured, or stressed non-apoptotic cells, with multiple roles in inflammation and immunity. Release of DAMPs not only contributes to tumor growth and progression but also mediates skewing of antitumor immunity during so-called immunogenic tumor cell death (ICD). Autophagy is a lysosome-mediated homeostatic degradation process in which cells digest their own effete organelles and macromolecules to meet bioenergetic needs and enable protein synthesis. For tumor cells, autophagy is a double-edged sword. Autophagy, in balance with apoptosis, can function as a tumor suppressor; autophagy deficiency, associated with alterations in apoptosis, initiates tumorigenesis in many settings. In contrast, autophagy-related stress tolerance generally promotes cell survival, which enables tumor growth and promotes therapeutic resistance. Most anticancer therapies promote DAMP release and enhance autophagy. Autophagy not only regulates DAMP release and degradation, but also is triggered and regulated by DAMPs. This interplay between autophagy and DAMPs, serving as 'strange attractors' in the dynamic system that emerges in cancer, regulates the effectiveness of antitumor treatment. This interplay also shapes the immune response to dying cells upon ICD, culling the least fit tumor cells and promoting survival of others. Thus, DAMPs and autophagy are suitable emergent targets for cancer therapy, considering their more nuanced role in tumor progression.
AB - Resistance to 'apoptotic' cell death is one of the major hallmarks of cancer, contributing to tumor development and therapeutic resistance. Damage-associated molecular patterns (DAMPs) are molecules released or exposed by dead, dying, injured, or stressed non-apoptotic cells, with multiple roles in inflammation and immunity. Release of DAMPs not only contributes to tumor growth and progression but also mediates skewing of antitumor immunity during so-called immunogenic tumor cell death (ICD). Autophagy is a lysosome-mediated homeostatic degradation process in which cells digest their own effete organelles and macromolecules to meet bioenergetic needs and enable protein synthesis. For tumor cells, autophagy is a double-edged sword. Autophagy, in balance with apoptosis, can function as a tumor suppressor; autophagy deficiency, associated with alterations in apoptosis, initiates tumorigenesis in many settings. In contrast, autophagy-related stress tolerance generally promotes cell survival, which enables tumor growth and promotes therapeutic resistance. Most anticancer therapies promote DAMP release and enhance autophagy. Autophagy not only regulates DAMP release and degradation, but also is triggered and regulated by DAMPs. This interplay between autophagy and DAMPs, serving as 'strange attractors' in the dynamic system that emerges in cancer, regulates the effectiveness of antitumor treatment. This interplay also shapes the immune response to dying cells upon ICD, culling the least fit tumor cells and promoting survival of others. Thus, DAMPs and autophagy are suitable emergent targets for cancer therapy, considering their more nuanced role in tumor progression.
KW - DAMPs
KW - apoptosis
KW - autophagy
KW - cancer
KW - immunity
KW - necrosis
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U2 - 10.1038/cddis.2013.493
DO - 10.1038/cddis.2013.493
M3 - Review article
C2 - 24336086
AN - SCOPUS:84891754287
SN - 2041-4889
VL - 4
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 12
M1 - e966
ER -