Abstract
Simple SummaryBoth cancer cells and immune cells depend on specific metabolic programs for their survival and function. Depending on which metabolic changes occur, immune cells can either promote or suppress the antitumor immune response. This review summarizes the metabolic pathways that polarize innate immune cells for immune activation or suppression and describes the current clinical applications of these findings.Cancer cells possess specific metabolic requirements for their survival, proliferation, and progression. Within a shared microenvironment, immune cells depend on competing metabolic pathways for their development and effector function. As a result, local acidification, hypoxia, and nutrient depletion in the tumor microenvironment can alter the antitumor immune response and even promote resistance to immunotherapies such as immune checkpoint blockade and adoptive cell transfer. Although T cells are the primary effectors of the antitumor response, growing evidence demonstrates that innate immune cells are critical to successful tumor clearance. This review aims to summarize current research related to the innate immune system, metabolism, and cancer. We first discuss the specific metabolic requirements of innate immune cells for immune activation and suppression and conclude by highlighting ongoing clinical applications of these findings.
Highlights
Decades of research have demonstrated the role of metabolic adaptations for cancer cell survival, proliferation, and progression [1,2,3]
Since T cells have received the most attention to date as the immediate effectors of most immunotherapies, this review aims to summarize current research related to the innate immune system, metabolism, and cancer [10,11,12]
Specific subsets of Dendritic cells (DCs) include conventional DCs, which play a crucial role in promoting antitumor CD4+ and CD8+ T cell responses, and plasmacytoid DCs, which have been linked to immunosuppression and tolerance [15,16,17,18,19]
Summary
Decades of research have demonstrated the role of metabolic adaptations for cancer cell survival, proliferation, and progression [1,2,3]. In a variety of immune cell subtypes, increased glycolysis leads to immune activation, whereas increases in fatty acid oxidation, oxidative phosphorylation, and lipid uptake contribute to immune suppression These metabolic alterations and ultimate impact on the local tumor microenvironment are cell type and context dependent. A greater understanding of the mechanisms underlying the interplay be and immune cell metabolism is important to understand given the of immunotherapies such as adoptive cell therapy and immune checkpoint bloc the success of these treatments, many patients do not respond, and others rel initial period of response [7,8]. This paper first discusses the specific metabolic requireme immune cells for immune activation and suppression and summarizes them in paper concludes by highlighting ongoing clinical applications of these findings. CARKL—carbohydrate kinase-like protein; cMYC-HIF-1α— hypoxia inducible factor 1-alpha; IKKE—IkB kinase-E; iNOS— inducible nitric oxide synthase; mTOR—mammalian target of rapamycin; OxPHOS—oxidative phosphorylation; PGE2—prostaglandin E2; PI3K—phosphatidylinositol 3-kinase; PPAR—peroxisome proliferator-activated receptor; SREBP1—sterol regulatory element binding protein; TBK1—tank binding kinase 1
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