Autophagy inhibition in cancer therapy: metabolic considerations for antitumor immunity
- 14 August 2012
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 249 (1), 176-194
- https://doi.org/10.1111/j.1600-065x.2012.01141.x
Abstract
Summary: Tumors and the immune system are intertwined in a competition where tilting the fine balance between tumor‐specific immunity and tolerance can ultimately decide the fate of the host. Defensive and suppressive immunological responses to cancer are exquisitely sensitive to metabolic features of rapidly growing tumors, such as hypoxia, low nutrient availability, and aberrant growth factor signaling. As a result, clinical therapies impacting these properties change the in situ antitumor immune response by virtue of disrupting the tumor environment. To compensate for disruptions in cellular metabolism, cells activate autophagy to promote survival. On the basis of this notion, strategies designed to block autophagy in tumor cells are currently being tested in several human clinical trials. However, therapies that impair tumor metabolism must also take into account their effect on lymphocytes activated in the immune response to cancer. Given that a strong antitumor immune response is a positive prognostic factor in overall patient survival, identifying ways to block essential processes in tumor cells and suppressive immune cells while promoting those that are important for a robust immune response are of critical importance. Herein, we review the effects of anti‐cancer agents that impact metabolism administered concurrently with autophagy inhibitors on immune cells and consider the implications for patient response to therapy.Keywords
This publication has 102 references indexed in Scilit:
- Reply to: Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune systemNature Medicine, 2012
- Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2)Diabetologia, 2012
- Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1Cell, 2011
- Aberrant CD8+ T-Cell Responses and Memory Differentiation upon Viral Infection of an Ataxia-Telangiectasia Mouse Model Driven by Hyper-Activated Akt and mTORC1 SignalingThe American Journal of Pathology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Molecular determinants of immunogenic cell death elicited by anticancer chemotherapyCancer and Metastasis Reviews, 2011
- Cell Signaling by Receptor Tyrosine KinasesCell, 2010
- Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant MetastasisCancer Cell, 2009
- Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cellsEuropean Journal of Immunology, 2008
- AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3Biochemical Pharmacology, 2006