Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer. (November 2022)

• Record Type: Journal Article
• Authors: Wang, Yi; Wang, Yuya; Ren, Yifei; Zhang, Qi; Yi, Ping; Cheng, Chunming
• Is Part Of: Seminars in cancer biology. Volume 86(2023)Part 3
• Page Start: 542
• Page End: 565
• Publication Date: 2022-11
• Subjects: 4-1BB/TNFRSF9 Recombinant tumor necrosis factor ligand superfamily member 9 -- 4-1BBL 4-1BB ligand -- APC :Antigen-presenting cell -- B7 B7 family (including B7-1 [CD80], B7-2 [CD86], B7-H1/PD-L1 [CD274], B7-H2/ICOSL [CD275], B7-H3 [CD276], B7-H4, B7-H6, B7-DC/PD-L2 [CD273]) -- CD Cluster of differentiation -- CTLA-4 Cytotoxic T-lymphocyte-associated protein 4 -- DC Dendritic cells -- Gal-9 Galectin-9 -- GITR Glucocorticoid-induced tumor necrosis factor receptor -- GITRL Glucocorticoid-induced tumor necrosis factor receptor ligand -- ICOS Inducible costimulatory -- ICOSL Inducible costimulator ligand -- IDO Indoleamine 2: 3-dioxygenase -- IFN-γ Interferon γ -- IL Interleukin -- KIR Killer-cell immunoglobulin-like receptors -- LAG-3 Lymphocyte-activation gene 3 -- M2 Macrophage: Alternatively activated macrophage -- MHC-I Major histocompatibility complex class I -- MHC-II Major histocompatibility complex class II -- MMPs Matrix metalloproteinases -- NCR Natural cytotoxicity receptor -- NK cell Natural killer cell -- NKG2D Natural-killer group 2: member D -- OX40/TNFRSF4 Tumor necrosis factor receptor superfamily member 4 -- OX40L OX40 ligand -- PD-1 Programmed cell death 1 -- PD-L1 Programmed cell death ligand-1 -- PD-L2 Programmed cell death ligand-2 -- PLT Platelet -- TCR T cell receptor -- TGF-β Transforming growth factor-β -- Th1 T helper 1 cell -- Th2 T helper 2 cell -- TIM-3 T cell immunoglobulin domain and mucin domain-3 -- Treg Regulatory T cells -- VEGF Vascular endothelial growth factor -- VISTA V-domain immunoglobulin suppressor of T-cell activation -- A2aR Adenosine receptor A2A -- ADI-PEG20 Pegylated arginine deiminase -- AML Acute myeloid leukemias -- BET Bromodomain and extra-terminal motif -- BCG Bacillus calumette-guerin -- COX Cyclooxygenase -- EP4 Prostaglandin E2 receptor 4 -- EPT Electroporation therapy -- GITR Glucocorticoid-induced TNFR-related protein -- GLS Glutaminase -- GIST Gastrointestinal stromal tumors -- HNSCC head and neck squamous cell carcinoma -- IDH1 isocitrate dehydrogenase 1 -- IDO Indoleamine 2:3-dioxygenase -- KIR2D Killer immunoglobulin-like receptor -- LSD1 Lysine-specific demethylase 1A -- MDS Myelodysplastic syndromes -- MIBC : Muscle-invasive bladder cancer -- NMIBC Non-muscle invasive bladder cancer -- NSCLC Non-small-cell lung cancer -- PGE2 Prostaglandin E2 -- PPI Proton pump inhibitor -- RCC Renal cell carcinoma -- SBRT Stereotactic body radiotherapy -- SCLC Small-cell lung cancer -- TIGIT T cell immunoglobulin and ITIM domain -- TNBC Triple negative breast cancer -- VEGF Vascular endothelial-derived growth factor -- FA Fatty acid -- LD Lipid droplet -- CE Cholesterol ester; Immune checkpoint -- Tumor metabolism -- Immunotherapy -- Tumor microenvironment -- Glycolysis -- Amine acid metabolism -- Lipid metabolism -- Fatty acid synthesis; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2022.02.010
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) or programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)–based immune checkpoint inhibitors (ICIs) have led to significant improvements in the overall survival of patients with certain cancers and are expected to benefit patients by achieving complete, long-lasting remissions and cure. However, some patients who receive ICIs either fail treatment or eventually develop immunotherapy resistance. The existence of such patients necessitates a deeper understanding of cancer progression, specifically nutrient regulation in the tumor microenvironment (TME), which includes both metabolic cross-talk between metabolites and tumor cells, and intracellular metabolism in immune and cancer cells. Here we review the features and behaviors of the TME and discuss the recently identified major immune checkpoints. We comprehensively and systematically summarize the metabolic modulation of tumor immunity and immune checkpoints in the TME, including glycolysis, amino acid metabolism, lipid metabolism, and other metabolic pathways, and further discuss the potential metabolism-based therapeutic strategies tested in preclinical and clinical settings. These findings will help to determine the existence of a link or crosstalk between tumor metabolism and immunotherapy, which will provide an important insight into cancer treatment and cancer research.