Abstract
Simple SummarySubstantial effort has been made in recent years to improve the clinical outcome of cancer immunotherapy. Recent findings suggest that manipulation of glucose metabolism can represent a valuable tool to limit cancer cell growth and to help the immune system to elicit an efficient and protective response to cancer cells. Both pharmacological approaches and diets with a low carbohydrate content are under evaluation in order to limit glucose availability in metabolic processes for a future application as co-adjuvant strategies to improve cancer immunotherapies.The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathway is central in shaping T cell responses and emerges as an ideal target to improve cancer immunotherapy. However, metabolic manipulation requires a deep level of control over side-effects and development of biomarkers of response. Here, we summarize the metabolic control of T cell function and focus on the implications of metabolic manipulation for the design of immunotherapeutic strategies. Integrating our understanding of T cell function and metabolism will hopefully foster the forthcoming development of more effective immunotherapeutic strategies.
Highlights
Targeting metabolic pathways is emerging as a potent strategy to manipulate immune responses against cancer [1]
Glucose metabolism through the glycolytic pathway is central in shaping T cell responses and is an ideal target to improve cancer immunotherapy
hypoxia-inducible transcription factor (HIF)-1a prevents glucose-derived pyruvate from mitochondrial oxidation and promotes glycolysis which is associated with a reduced suppressive function [42]
Summary
Targeting metabolic pathways is emerging as a potent strategy to manipulate immune responses against cancer [1]. Transferred T cells are a potent therapeutic tool for the eradication of established tumors and provide long-term immunity, protecting the individual from disease recurrence [2] Both the effector function and generation of memory responses are intimately linked to specific metabolic processes [3], suggesting that the Cancers 2020, 12, 2940; doi:10.3390/cancers12102940 www.mdpi.com/journal/cancers. Tumor cells are often dependent on glucose as a primary energy source, due to their extensive proliferation that necessitates uninterrupted access to energy and the building blocks of cellular biomass To meet these requirements, cancer cells utilize glycolysis, even in the presence of oxygen, a process referred to as aerobic glycolysis or the “Warburg effect”. Metabolic targeting is not meant to affect a specific cell but rather the metabolic processes that sustain disease progression
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