A new aspect of an old friend: the beneficial effect of metformin on anti-tumor immunity
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-Tcells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.
Abstract
T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-Tcells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.
참고문헌 (94)
- Irons BK, "Drug treatment of type 2diabetes mellitus in patients for whom metformin is contraindicated", Diabetes Metab Syndr Obes, 7, pp.15~24 (2014)
- Evans JM, "Metformin and reduced risk of cancer in diabetic patients", BMJ, 330, pp.1304~1305 (2005)
- Viollet B, "Cellular and molecular mechanisms of metformin : an overview", Clin Sci (Lond), 22, pp.253~270 (2012)
- Aljofan M, "Anticancer activity of metformin : a systematic review of the literature", Future Sci OA, 5, pp.FSO410~ (2019)
- Dowling RJ, "Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells", Cancer Res, 67, pp.10804~10812 (2007)
- Andrzejewski S, "Metabolic Profiles Associated With Metformin Efficacy in Cancer", Front Endocrinol (Lausanne), 9, pp.372~ (2018)
- Tseng HW, "Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression", Cancers (Basel), 11, pp.209~ (2019)
- Deng XS, "Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers", Cell Cycle, 11, pp.367~376 (2012)
- Feng Y, "Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling", Cell Death Dis, 5, pp.e1088~ (2014)
- Eikawa S, "Immune-mediated antitumor effect by type 2 diabetes drug, metformin", Proc Natl Acad Sci U S A, 112, pp.1809~1814 (2015)
- Cha JH, "Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1", Mol Cell, 71, pp.606~620e607 (2018)
- Garcia EY, "Flumamine, a new synthetic analgesic and anti-flu drug", J Philipp Med Assoc, 26, pp.287~293 (1950)
- Zhang Z, "Metformin Enhances the Antitumor Activity of CD8(+)T Lymphocytes via the AMPKmiR-107-Eomes-PD-1 Pathway", J Immunol, 204, pp.2575~2588 (2020)
- Cha JH, "New Approaches on Cancer Immunotherapy", Cold Spring Harb Perspect Med, 10, pp.a036863~ (2019)
- Del Barco S, "Metformin : multi-faceted protection against cancer", Oncotarget, 2, pp.896~917 (2011)
- Basu AK, "DNA Damage, Mutagenesis and Cancer", Int J Mol Sci, 19, pp.970~ (2018)
- Hyndman IJ, "Review : the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours", Cancer Microenviron, 9, pp.63~69 (2016)
- Mittal D, "New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape", Curr Opin Immunol, 27, pp.16~25 (2014)
- Paul S, "The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy", Front Immunol, 8, pp.1124~ (2017)
- Reeves E, "Antigen processing and immune regulation in the response to tumours", Immunology, 150, pp.16~24 (2017)
- Kim R, "Cancer immunoediting from immune surveillance to immune escape", Immunology, 121, pp.1~14 (2007)
- de Charette M, "Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy?", Eur J Cancer, 68, pp.134~147 (2016)
- Halenius A, "Classical and non-classical MHC I molecule manipulation by human cytomegalovirus: so many targets-but how many arrows in the quiver?", Cell Mol Immunol, 12, pp.139~153 (2015)
- Kochan G, "Role of non-classical MHC class I molecules in cancer immunosuppression", Oncoimmunology, 2, pp.e26491~ (2013)
- Balkwill FR, "The tumor microenvironment at a glance", J Cell Sci, 125, pp.5591~5596 (2012)
- Gajewski TF, "Innate and adaptive immune cells in the tumor microenvironment", Nat Immunol, 14, pp.1014~1022 (2013)
- Wang M, "Role of tumor microenvironment in tumorigenesis", J Cancer, 8, pp.761~773 (2017)
- Quail DF, "Microenvironmental regulation of tumor progression and metastasis", Nat Med, 19, pp.1423~1437 (2013)
- Kambayashi T, "Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?", Nat Rev Immunol, 14, pp.719~730 (2014)
- Hagemann T, "Inflammation and cancer : a double-edged sword", Cancer Cell, 12, pp.300~301 (2007)
- Zitvogel L, "Nutrition, inflammation and cancer", Nat Immunol, 18, pp.843~850 (2017)
- Dranoff G, "Cytokines in cancer pathogenesis and cancer therapy", Nat Rev Cancer, 4, pp.11~22 (2004)
- Poh AR, "Targeting Macrophages in Cancer : From Bench to Bedside", Front Oncol, 8, pp.49~ (2018)
- Landskron G, "Chronic inflammation and cytokines in the tumor microenvironment", J Immunol Res, 2014, pp.149185~ (2014)
- D'Elia RV, "Targeting the"cytokine storm"for therapeutic benefit", Clin Vaccine Immunol, 20, pp.319~327 (2013)
- Kumar V, "The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment", Trends Immunol, 37, pp.208~220 (2016)
- Hanson EM, "Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells", J Immunol, 183, pp.937~944 (2009)
- Crusz SM, "Inflammation and cancer : advances and new agents", Nat Rev Clin Oncol, 12, pp.584~596 (2015)
- Brasky TM, "Non-steroidal anti-inflammatory drugs and cancer incidence by sex in the VITamins And Lifestyle(VITAL)cohort", Cancer Causes Control, 23, pp.431~444 (2012)
- Liu Y, "Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality : a systematic review and meta-analysis", BMC Med, 12, pp.55~ (2014)
- Nath N, "Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis", J Immunol, 182, pp.8005~8014 (2009)
- Triggle CR, "Cardiovascular impact of drugs used in the treatment of diabetes", Ther Adv Chronic Dis, 5, pp.245~268 (2014)
- Lund SS, "Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2diabetes", Eur J Endocrinol, 158, pp.631~641 (2008)
- Huang NL, "Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation", Int J Cardiol, 134, pp.169~175 (2009)
- Ersoy C, "The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients", Diabetes Res Clin Pract, 81, pp.56~60 (2008)
- Kelly B, "Metformin Inhibits the Production of Reactive Oxygen Species from NADH : Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta(IL-1beta)and Boosts Interleukin-10(IL-10)in Lipopolysaccharide(LPS)-activated Macrophages", J Biol Chem, 290, pp.20348~20359 (2015)
- Wang JC, "Metformin's antitumour and anti-angiogenic activities are mediated by skewing macrophage polarization", J Cell Mol Med, 22, pp.3825~3836 (2018)
- Qin G, "Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis", Oncoimmunology, 7, pp.e1442167~ (2018)
- Semenza GL, "The hypoxic tumor microenvironment : A driving force for breast cancer progression", Biochim Biophys Acta, 1863, pp.382~391 (2016)
- Brown JM, "The hypoxic cell : a target for selective cancer therapy--eighteenth Bruce F. Cain Memorial Award lecture", Cancer Res, 59, pp.5863~5870 (1999)
- Eales KL, "Hypoxia and metabolic adaptation of cancer cells", Oncogenesis, 5, pp.e190~ (2016)
- Weidemann A, "Biology of HIF-1alpha", Cell Death Differ, 15, pp.621~627 (2008)
- Subarsky P, "The hypoxic tumour microenvironment and metastatic progression", Clin Exp Metastasis, 20, pp.237~250 (2003)
- Noman MZ, "Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response", Crit Rev Immunol, 31, pp.357~377 (2011)
- Clambey ET, "Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa", Proc Natl Acad Sci U S A, 109, pp.E2784~E2793 (2012)
- Mancino A, "Divergent effects of hypoxia on dendritic cell functions", Blood, 112, pp.3723~3734 (2008)
- Vuillefroy de Silly R, "Hypoxia and antitumor CD8+ T cells: An incompatible alliance?", Oncoimmunology, 5, pp.e1232236~ (2016)
- Wang JC, "Suppression of hypoxia-induced excessive angiogenesis by metformin via elevating tumor blood perfusion", Oncotarget, 8, pp.73892~73904 (2017)
- Zhou X, "Metformin suppresses hypoxia-induced stabilization of HIF-1alpha through reprogramming of oxygen metabolism in hepatocellular carcinoma", Oncotarget, 7, pp.873~884 (2016)
- Guimaraes TA, "Metformin increases PDH and suppresses HIF-1alpha under hypoxic conditions and induces cell death in oral squamous cell carcinoma", Oncotarget, 7, pp.55057~55068 (2016)
- Scharping NE, "Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia", Cancer Immunol Res, 5, pp.9~16 (2017)
- Thompson RH, "Costimulatory B7-H1 in renal cell carcinoma patients : Indicator of tumor aggressiveness and potential therapeutic target", Proc Natl Acad Sci U S A, 101, pp.17174~17179 (2004)
- Zhang M, "PD-L1 expression in lung cancer and its correlation with driver mutations : a meta-analysis", Sci Rep, 7, pp.10255~ (2017)
- Brody R, "PD-L1 expression in advanced NSCLC : Insights into risk stratification and treatment selection from a systematic literature review", Lung Cancer, 112, pp.200~215 (2017)
- Li J, "Prognostic value of programmed cell death ligand 1 expression in patients with head and neck cancer : A systematic review and metaanalysis", PLoS One, 12, pp.e0179536~ (2017)
- Schildberg FA, "Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family", Immunity, 44, pp.955~972 (2016)
- Pardoll DM, "The blockade of immune checkpoints in cancer immunotherapy", Nat Rev Cancer, 12, pp.252~264 (2012)
- Verdura S, "Metformin as an archetype immuno-metabolic adjuvant for cancer immunotherapy", Oncoimmunology, 8, pp.e1633235~ (2019)
- Han Y, "Metformin reverses PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in triple-negative breast cancer", Am J Cancer Res, 9, pp.800~815 (2019)
- Garner H, "Immune crosstalk in cancer progression and metastatic spread : a complex conversation", Nat Rev Immunol, 20, pp.483~497 (2020)
- Voss K, "Metabolic reprogramming and apoptosis sensitivity : Defining the contours of a T cell response", Cancer Lett, 408, pp.190~196 (2017)
- Burns JS, "Metabolic Pathways of the Warburg Effect in Health and Disease : Perspectives of Choice, Chain or Chance", Int J Mol Sci, 18, pp.2755~ (2017)
- Almeida L, "Metabolic pathways in T cell activation and lineage differentiation", Semin Immunol, 28, pp.514~524 (2016)
- Afonso J, "Competitive glucose metabolism as a target to boost bladder cancer immunotherapy", Nat Rev Urol, 17, pp.77~106 (2020)
- Garza-Lombo C, "mTOR", AMPK signaling in the brain : Cell metabolism, proteostasis and survival, 2018, pp.8, 102~110
- Blagih J, "The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo", Immunity, 42, pp.41~54 (2015)
- Rao E, "Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death", Oncotarget, 6, pp.7944~7958 (2015)
- Pollizzi KN, "mTORC1 and mTORC2 selectively regulate CD8(+)T cell differentiation", J Clin Invest, 125, pp.2090~2108 (2015)
- Pennock ND, "T cell responses : naive to memory and everything in between", Adv Physiol Educ, 37, pp.273~283 (2013)
- van der Windt GJ, "Metabolic switching and fuel choice during T-cell differentiation and memory development", Immunol Rev, 249, pp.27~42 (2012)
- Rolf J, "AMPKalpha1 : a glucose sensor that controls CD8 T-cell memory", Eur J Immunol, 43, pp.889~896 (2013)
- Araki K, "mTOR regulates memory CD8 T-cell differentiation", Nature, 460, pp.108~112 (2009)
- Durack J, "The gut microbiome : Relationships with disease and opportunities for therapy", J Exp Med, 216, pp.20~40 (2019)
- Xu H, "The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases", J Immunol Res, 2019, pp.7546047~ (2019)
- Balakrishnan B, "Microbial modulation of the gut microbiome for treating autoimmune diseases", Expert Rev Gastroenterol Hepatol, 12, pp.985~996 (2018)
- Gopalakrishnan V, "Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients", Science, 359, pp.97~103 (2018)
- Matson V, "The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients", Science, 359, pp.104~108 (2018)
- Routy B, "Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors", Science, 359, pp.91~97 (2018)
- de la Cuesta-Zuluaga J, "Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut", Diabetes Care, 40, pp.54~62 (2017)
- Feng W, "Gut Microbiota, Short-Chain Fatty Acids, and Herbal Medicines", Front Pharmacol, 9, pp.1354~ (2018)
- Parada Venegas D, "Short Chain Fatty Acids(SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases", Front Immunol, 10, pp.277~ (2019)
- Waldman AD, "A guide to cancer immunotherapy : from T cell basic science to clinical practice", Nat Rev Immunol, 20, pp.1~18 (2020)
- Duan Q, "Turning Cold into Hot : Firing up the Tumor Microenvironment", Trends Cancer, 6, pp.605~618 (2020)
- Bonaventura P, "Cold Tumors : A Therapeutic Challenge for Immunotherapy", Front Immunol, 10, pp.168~ (2019)
