Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 1, Pages 173-193Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-020-03581-0
Keywords
Antitumor immunotherapy; Immune checkpoint; Tumor metabolism; Metabolic reprogramming; Metabolic checkpoint
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Funding
- National Natural Science Foundation of China [81903138, 81972776, 81803025, 81772928, 81702907, 81772901, 81672993, 81672683]
- Natural Science Foundation of Hunan Province [2019JJ50778, 2018SK21210, 2018SK21211, 2018JJ3704, 2018JJ3815]
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This review summarizes the metabolic reprogramming of various cell types in the tumor microenvironment, focusing on the interaction between the metabolic pathways of these cells and antitumor immunosuppression, as well as discussing potential new approaches to enhance antitumor immunotherapy through metabolic checkpoints.
The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activation and effector function of immune cells through a variety of mechanisms; in turn, the metabolites and other factors secreted by immune cells can also become accomplices to cancer development. Immune-metabolic checkpoint regulation is an emerging concept that is being studied with the aim of restoring the immune response in the tumor microenvironment. In this review, we summarize the metabolic reprogramming of various cell types present in the tumor microenvironment, with a focus on the interaction between the metabolic pathways of these cells and antitumor immunosuppression. We also discuss the main metabolic checkpoints that could provide new means of enhancing antitumor immunotherapy.
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