When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

Katrin Schlie,Luke R K Hughson,Julian J Lum,Jaeline E Spowart,Katelin N Townsend

doi:10.1155/2011/470597

Katrin Schlie, Luke R K Hughson + Show 3 more

Open Access

https://doi.org/10.1155/2011/470597

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Abstract

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

Highlights

In many tumors, cell growth and proliferation exceeds the development of local vasculature supplying oxygen and nutrients
In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system
The tumor microenvironment is complex, comprised of a variety of factors that can act on all cells including immune and cancer cells (Figure 4)

Summary

Introduction

Cell growth and proliferation exceeds the development of local vasculature supplying oxygen and nutrients. Cancer cells in close proximity to vasculature contribute to tumor hypoxia by rapidly utilizing oxygen and nutrients that arrive at the tumor site. This can result in either chronic or cycling hypoxia depending on how quickly cancer cells consume oxygen once new vascular networks are formed [3, 4]. As a result of hypoxic stress, cells in the tumor microenvironment activate autophagy, a cell survival process that degrades and recycles cellular constituents. Selective or bulk portions of cytoplasm, including whole organelles, are sequestered in double-membraned vacuoles called autophagosomes These structures fuse with lysosomes to form autophagolysosomes, the site of degradation for the sequestered cargo. Understanding the physiological consequences of autophagy in different cell types in the tumor microenvironment is critical when considering therapies that target autophagy

Hypoxia-Induced Autophagy in Tumor Cells

Autophagy in Immune Cells in a Hypoxic Tumor Environment

Conclusion