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Autophagy and the Tumor Microenvironment

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Autophagy and Cancer

Part of the book series: Current Cancer Research ((CUCR,volume 8))

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Abstract

Malignant cells do not act as separate entities; they exist in the context of an emergent microenvironment that they create in concert with the host over several years of intimate interaction. The tumor microenvironment (TME) is composed of inflammatory/immune cells, endothelial cells, fibroblasts, cytokines, chemokines, growth factors and the extracellular matrix. The TME has been implicated in the regulation of tumor initiation and progression, determining metastatic potential, and impacting the response to therapy. The TME is highly dynamic and contains subpopulations of cancer cells with temporally varying gradients of cellular metabolism, O2 content, pH, genomic stability and a propensity for aggressive behavior. The stressors present within the TME, include hypoxia, low nutrient availability, immune infiltrates, inflammatory factors and unscheduled cell death associated with release of endogenous damage associated molecular pattern (DAMP) molecules. DAMPs, including the chromatin-binding protein high mobility group box 1 (HMGB1), alert the host of tissue damage or injury by triggering immune responses and activating stress mechanisms such as autophagy through their interaction with pattern recognition receptors. Autophagy, a conserved lysosomal degradation pathway, is a cell maintenance program that is operative at basal levels in all cells, extinguishing during traversion of the cell cycle. It is invoked at higher levels as a survival mechanism in response to environmental and cellular stress. The role of autophagy in cancer including the TME is complex and may differ depending on tumor type or context. In this chapter, recent advances in our understanding of autophagic molecular mechanisms and functions in the TME are reviewed.

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Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Daolin Tang

  2. Department of Surgery, Immunology and Bioengineering, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Michael T. Lotze

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  1. Daolin Tang
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  2. Michael T. Lotze
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Correspondence to Daolin Tang or Michael T. Lotze .

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  1. Penn State College of Medicine, Pharmacology, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, 17033, Pennsylvania, USA

    Hong-Gang Wang

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Tang, D., Lotze, M.T. (2013). Autophagy and the Tumor Microenvironment. In: Wang, HG. (eds) Autophagy and Cancer. Current Cancer Research, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6561-4_9

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