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Autophagy in tumour immunity and therapy

Abstract

Autophagy is a regulated mechanism that removes unnecessary or dysfunctional cellular components and recycles metabolic substrates. In response to stress signals in the tumour microenvironment, the autophagy pathway is altered in tumour cells and immune cells — thereby differentially affecting tumour progression, immunity and therapy. In this Review, we summarize our current understanding of the immunologically associated roles and modes of action of the autophagy pathway in cancer progression and therapy, and discuss potential approaches targeting autophagy to enhance antitumour immunity and improve the efficacy of current cancer therapy.

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Fig. 1: The machinery of canonical and non-canonical autophagy.
Fig. 2: Impact of tumour autonomous autophagy on immunity.
Fig. 3: Autophagy in immune cells in the tumour microenvironment.
Fig. 4: Targeting autophagy for tumour immunotherapy.

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Acknowledgements

The authors thank their trainees from the Zou and Green labs, as well as collaborators for their scientific input. This work was supported in part by research grants from the US National Institutes of Health (NIH) (AI40646 and CA231620 to D.R.G., and CA217648, CA123088, CA099985, CA193136 and CA152470 to W.Z.), the NCI Cooperative Human Tissue Network (CHTN) and the NIH through the University of Michigan Rogel Cancer Center Grant (P30 CA046592).

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H.X., D.R.G. and W.Z. wrote the manuscript.

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Glossary

Immunogenicity

The ability to provoke an immune response in humans or other animals.

Chimeric antigen receptor T cells

(CAR T cells). Cells used in a type of cancer treatment in which the patient’s T cells are modified in the laboratory to carry CAR and reinfused back into the patient to attack cancer cells recognized by CAR.

Oxidative phosphorylation

The electron transfer chain driven by substrate oxidation that is coupled to the synthesis of ATP through an electrochemical transmembrane gradient.

Autophagic flux

The measure of autophagic degradation activity.

Reactive oxygen species

(ROS). The highly reactive form of molecular oxygen formed as a by-product during the metabolism of oxygen.

Damage-associated molecular patterns

(DAMPs). Host-derived molecules that can initiate a non-infectious inflammatory response.

Epithelial–mesenchymal transition

A reversible cellular programme in which epithelial cells lose their cell polarity and cell–cell adhesion, gain migratory and invasive properties, and, finally, are transformed into mesenchymal cells.

The Cancer Genome Atlas

(TCGA). A project to catalogue genetic mutations responsible for cancer that takes advantage of genome sequencing and bioinformatics.

Senescence

A process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing cell death.

Clustered regularly interspaced short palindromic repeats

(CRISPR). A family of repetitive DNA sequence used to detect and destroy DNA.

Glycolysis

The metabolic pathway that converts glucose into pyruvate independent of oxygen.

Fatty acid β-oxidation

The catabolic process by which fatty acid molecules are broken down to generate acetyl-coenzyme A (AcCoA) and utilized in the tricarboxylic acid (TCA) cycle.

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Xia, H., Green, D.R. & Zou, W. Autophagy in tumour immunity and therapy. Nat Rev Cancer 21, 281–297 (2021). https://doi.org/10.1038/s41568-021-00344-2

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