title: Strange attractors: DAMPs and autophagy link tumor cell death and immunity.
abstract: 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.
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: W
authors: W
authors: Hou
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: Q
authors: Q
authors: Zhang
authors: 1] Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA [2] Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors: Z
authors: Z
authors: Yan
authors: 1] Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA [2] Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: R
authors: R
authors: Chen
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: H J
authors: HJ
authors: Zeh Iii
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: R
authors: R
authors: Kang
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: M T
authors: MT
authors: Lotze
authors: Department of Surgery-DAMP Laboratory, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh 15213, PA, USA.
authors: D
authors: D
authors: Tang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology / Q000502:physiology*; D016923:Cell Death / Q000276:immunology* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*