Mitochondrial metabolism: Inducer or therapeutic target in tumor immune-resistance?. (February 2020)

• Record Type: Journal Article
• Authors: Kopecka, Joanna; Gazzano, Elena; Castella, Barbara; Salaroglio, Iris C.; Mungo, Eleonora; Massaia, Massimo; Riganti, Chiara
• Is Part Of: Seminars in cell & developmental biology. Volume 98(2020)
• Page Start: 80
• Page End: 89
• Publication Date: 2020-02
• Subjects: OXPHOS oxidative phosphorylation -- FAO fatty acid β-oxidation -- TCA tricarboxylic acid -- ROS reactive oxygen species -- mt mitochondrial -- HIF-1α hypoxia inducible factor-1α -- VEGF vascular endothelial growth factor -- FAM49B family with sequence similarity 49 member B -- EMT epithelial-mesenchymal transition -- PGC-1α peroxisome proliferator-activated receptor-gamma coactivator-1α -- NO nitric oxide -- PNA peptide nucleic acids -- MHC major histocompatibility complex -- ICP immune-checkpoints -- TGF-β transforming growth factor-β -- IL-10 interleukin-10 -- CTL cytotoxic CD8+T-lymphocyte -- NK natural killer -- Treg T-regulatory -- MDSC myeloid-derived suppressor cell -- TAM tumor-associated macrophage -- mtDAMP mitochondrial danger-associated molecular pattern -- FPR formyl peptide receptor -- TLR-9 Toll-like receptor-9 -- ICD immunogenic cell death -- DC dendritic cell -- HMGB1 high mobility group box 1 -- TNF-α tumor necrosis factor-α -- NLRP3 NOD-like receptor containing pyrin domain 3 -- PD-1L programmed death-1 ligand -- STING stimulator of interferon genes -- IFN interferon -- IDO 23-indoleamine dioxygenase -- MitoVES mitochondria-targeted vitamin E succinate -- Pgp P-glycoprotein -- FPP farnesyl pyrophosphate -- ARG arginase -- NOS NO synthase -- TIL tumor-infiltrating lymphocyte -- GLUT1 glucose transporter-1 -- PDK1 pyruvate dehydrogenase kinase 1 -- CAD cis-aconitate decarboxylase -- IRG1 immune-responsive gene 1 -- SDH succinate dehydrogenase -- SUCNR1/GPR91 succinate receptor 1 -- LKB1 liver kinase B1 -- TCR T-cell receptor -- PHD prolyl hydroxylase -- AMPK adenosine monophosphate-activated protein kinase -- LPS lipopolysaccharide -- IL1Ra IL-1 receptor antagonist -- PKM2 pyruvate kinase M2 -- CIC citrate carrier; Mitochondrial metabolism -- Mitochondrial danger-associated molecular patterns -- Immunogenic cell death -- Tumor-induced immune-suppression -- Tumor-induced immune-escape; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2019.05.008
• Languages: English
• ISSNs: 1084-9521

Abstract

Highlights: Metabolites released from mitochondria help cancer cells to evade immune system. Effector and immune-suppressive cells have a different mitochondria metabolism. Targeting mitochondria metabolism in cancer cells can reverse immune-resistance. Modulating mitochondria metabolism activate or suppress immune cells activity. A precision medicine targeting mitochondria of cancer or immune subsets is needed. Abstract: Mitochondria have been considered for a long time only as the principal source of building blocks and energy upon aerobic conditions. Recently they emerged as key players in cell proliferation, invasion and resistance to therapy. The most aggressive tumors are able to evade the immune-surveillance. Alterations in the mitochondria metabolism either in cancer cells or in host immune system cells are involved in such tumor-induced immune-suppression. This review will focus on the main mitochondrial dysfunctions in tumor and immune cell populations determining immune-resistance, and on the therapies that may target mitochondrial metabolism and restore a powerful anti-tumor immune-activity.