Lactate modulates CD4
Acetylation
CD4-Positive T-Lymphocytes
/ immunology
Cancer-Associated Fibroblasts
/ metabolism
Forkhead Transcription Factors
/ metabolism
Humans
Immune Tolerance
Lactic Acid
/ metabolism
Male
MicroRNAs
/ metabolism
NF-kappa B
/ metabolism
Prostatic Neoplasms
/ immunology
Sirtuin 1
/ metabolism
T-Lymphocytes, Regulatory
/ immunology
Th1 Cells
/ immunology
Toll-Like Receptor 8
/ genetics
Tumor Microenvironment
/ immunology
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
02
08
2018
accepted:
25
12
2018
revised:
07
12
2018
pubmed:
22
1
2019
medline:
24
10
2019
entrez:
22
1
2019
Statut:
ppublish
Résumé
Leukocyte infiltration plays an active role in controlling tumor development. In the early stages of carcinogenesis, T cells counteract tumor growth. However, in advanced stages, cancer cells and infiltrating stromal components interfere with the immune control and instruct immune cells to support, rather than counteract, tumor malignancy, via cell-cell contact or soluble mediators. In particular, metabolites are emerging as active players in driving immunosuppression. Here we demonstrate that in a prostate cancer model lactate released by glycolytic cancer-associated fibroblasts (CAFs) acts on CD4
Identifiants
pubmed: 30664688
doi: 10.1038/s41388-019-0688-7
pii: 10.1038/s41388-019-0688-7
doi:
Substances chimiques
FOXP3 protein, human
0
Forkhead Transcription Factors
0
MIRN21 microRNA, human
0
MicroRNAs
0
NF-kappa B
0
TLR8 protein, human
0
Toll-Like Receptor 8
0
Lactic Acid
33X04XA5AT
SIRT1 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3681-3695Références
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37.
doi: 10.1038/nm.3394
Lyssiotis CA, Kimmelman AC. Metabolic interactions in the tumor microenvironment. Trends Cell Biol. 2017;27:863–75.
doi: 10.1016/j.tcb.2017.06.003
Anari F, Ramamurthy C, Zibelman M. Impact of tumor microenvironment composition on therapeutic responses and clinical outcomes in cancer. Future Oncol. 2018;14:1409–21.
doi: 10.2217/fon-2017-0585
Fiaschi T, Marini A, Giannoni E, Taddei ML, Gandellini P, De Donatis A, et al. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res. 2012;72:5130–40.
doi: 10.1158/0008-5472.CAN-12-1949
Giannoni E, Taddei ML, Morandi A, Comito G, Calvani M, Bianchini F, et al. Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread. Oncotarget. 2015;6:24061–74.
doi: 10.18632/oncotarget.4448
Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. 2016;9:5023–39.
doi: 10.2147/OTT.S105862
Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.
doi: 10.3389/fphar.2017.00561
Ludin A, Zon LI. Cancer immunotherapy: the dark side of PD-1 receptor inhibition. Nature. 2017;552:41–42.
doi: 10.1038/nature24759
Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014;20:61–72.
doi: 10.1016/j.cmet.2014.05.004
Biswas SK. Metabolic reprogramming of immune cells in cancer progression. Immunity. 2015;43:435–49.
doi: 10.1016/j.immuni.2015.09.001
Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic instruction of immunity. Cell. 2017;169:570–86.
doi: 10.1016/j.cell.2017.04.004
Sugiura A, Rathmell JC. Metabolic barriers to T cell function in tumors. J Immunol. 2018;200:400–7.
doi: 10.4049/jimmunol.1701041
Angelin A, Gil-de-Gómez L, Dahiya S, Jiao J, Guo L, Levine MH, et al. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Cell Metab. 2017;25:1282–93.e1287.
doi: 10.1016/j.cmet.2016.12.018
Geltink RIK, Kyle RL, Pearce EL. Unraveling the complex interplay between T cell metabolism and function. Annu Rev Immunol. 2018;36:461–88.
doi: 10.1146/annurev-immunol-042617-053019
Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513:559–63.
doi: 10.1038/nature13490
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109:3812–9.
doi: 10.1182/blood-2006-07-035972
Husain Z, Huang Y, Seth P, Sukhatme VP. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol. 2013;191:1486–95.
doi: 10.4049/jimmunol.1202702
Romero-Garcia S, Moreno-Altamirano MM, Prado-Garcia H, Sánchez-García FJ. Lactate contribution to the tumor microenvironment: mechanisms, effects on immune cells and therapeutic relevance. Front Immunol. 2016;7:52.
doi: 10.3389/fimmu.2016.00052
Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T, et al. Cancer acidity: an ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol. 2017;43:74–89.
doi: 10.1016/j.semcancer.2017.03.001
Morrot A, da Fonseca LM, Salustiano EJ, Gentile LB, Conde L, Filardy AA, et al. Metabolic symbiosis and immunomodulation: how tumor cell-derived lactate may dsturb innate and adaptive immune responses. Front Oncol. 2018;8:81.
doi: 10.3389/fonc.2018.00081
Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009;8:3984–4001.
doi: 10.4161/cc.8.23.10238
Saada A. Mitochondria: mitochondrial OXPHOS (dys) function ex vivo--the use of primary fibroblasts. Int J Biochem Cell Biol. 2014;48:60–65.
doi: 10.1016/j.biocel.2013.12.010
Sotgia F, Whitaker-Menezes D, Martinez-Outschoorn UE, Flomenberg N, Birbe RC, Witkiewicz AK, et al. Mitochondrial metabolism in cancer metastasis: visualizing tumor cell mitochondria and the “reverse Warburg effect” in positive lymph node tissue. Cell Cycle. 2012;11:1445–54.
doi: 10.4161/cc.19841
Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 2015;34:111.
doi: 10.1186/s13046-015-0221-y
Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41:211–8.
doi: 10.1016/j.tibs.2015.12.001
Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol. 2012;2012:762825.
doi: 10.1155/2012/762825
Su S, Liao J, Liu J, Huang D, He C, Chen F, et al. Blocking the recruitment of naive CD4. Cell Res. 2017;27:461–82.
doi: 10.1038/cr.2017.34
Ziani L, Chouaib S, Thiery J. Alteration of the antitumor immune response by cancer-associated fibroblasts. Front Immunol. 2018;9:414.
doi: 10.3389/fimmu.2018.00414
Costa A, Kieffer Y, Scholer-Dahirel A, Pelon F, Bourachot B, Cardon M, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell. 2018;33:463–79.e410.
doi: 10.1016/j.ccell.2018.01.011
Johnston CJ, Smyth DJ, Dresser DW, Maizels RM. TGF-β in tolerance, development and regulation of immunity. Cell Immunol. 2016;299:14–22.
doi: 10.1016/j.cellimm.2015.10.006
Neuzillet C, Tijeras-Raballand A, Cohen R, Cros J, Faivre S, Raymond E, et al. Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 2015;147:22–31.
doi: 10.1016/j.pharmthera.2014.11.001
Thompson ED, Enriquez HL, Fu YX, Engelhard VH. Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J Exp Med. 2010;207:1791–804.
doi: 10.1084/jem.20092454
Levine BL, Bernstein WB, Connors M, Craighead N, Lindsten T, Thompson CB, et al. Effects of CD28 costimulation on long-term proliferation of CD4 + T cells in the absence of exogenous feeder cells. J Immunol. 1997;159:5921–30.
pubmed: 9550389
Fang D, Zhu J. Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets. J Exp Med. 2017;214:1861–76.
doi: 10.1084/jem.20170494
Gambini J, Gomez-Cabrera MC, Borras C, Valles SL, Lopez-Grueso R, Martinez-Bello VE, et al. Free [NADH]/[NAD( + )] regulates sirtuin expression. Arch Biochem Biophys. 2011;512:24–29.
doi: 10.1016/j.abb.2011.04.020
Guarente L. Calorie restriction and sirtuins revisited. Genes Dev. 2013;27:2072–85.
doi: 10.1101/gad.227439.113
Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.
doi: 10.1038/nrm3293
van Loosdregt J, Brunen D, Fleskens V, Pals CE, Lam EW, Coffer PJ. Rapid temporal control of Foxp3 protein degradation by sirtuin-1. PLoS ONE. 2011;6:e19047.
doi: 10.1371/journal.pone.0019047
Sonveaux P, Copetti T, De Saedeleer CJ, Végran F, Verrax J, Kennedy KM, et al. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PLoS ONE. 2012;7:e33418.
doi: 10.1371/journal.pone.0033418
Végran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 2011;71:2550–60.
doi: 10.1158/0008-5472.CAN-10-2828
Polet F, Feron O. Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force. J Intern Med. 2013;273:156–65.
doi: 10.1111/joim.12016
Long M, Park SG, Strickland I, Hayden MS, Ghosh S. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity. 2009;31:921–31.
doi: 10.1016/j.immuni.2009.09.022
Ruan Q, Chen YH. Nuclear factor-κB in immunity and inflammation: the Treg and Th17 connection. Adv Exp Med Biol. 2012;946:207–21.
doi: 10.1007/978-1-4614-0106-3_12
Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109:E2110–2116.
doi: 10.1073/pnas.1209414109
Zhang Q, Helfand BT, Jang TL, Zhu LJ, Chen L, Yang XJ, et al. Nuclear factor-kappaB-mediated transforming growth factor-beta-induced expression of vimentin is an independent predictor of biochemical recurrence after radical prostatectomy. Clin Cancer Res. 2009;15:3557–67.
doi: 10.1158/1078-0432.CCR-08-1656
Giannoni E, Bianchini F, Calorini L, Chiarugi P. Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal. 2011;14:2361–71.
doi: 10.1089/ars.2010.3727
Montanari M, Rossetti S, Cavaliere C, D’Aniello C, Malzone MG, Vanacore D, et al. Epithelial-mesenchymal transition in prostate cancer: an overview. Oncotarget. 2017;8:35376–89.
doi: 10.18632/oncotarget.15686
Mendler AN, Hu B, Prinz PU, Kreutz M, Gottfried E, Noessner E. Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun activation. Int J Cancer. 2012;131:633–40.
doi: 10.1002/ijc.26410
Renner K, Singer K, Koehl GE, Geissler EK, Peter K, Siska PJ, et al. Metabolic hallmarks of tumor and immune cells in the tumor microenvironment. Front Immunol. 2017;8:248.
doi: 10.3389/fimmu.2017.00248
Gottfried E, Kunz-Schughart LA, Ebner S, Mueller-Klieser W, Hoves S, Andreesen R, et al. Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood. 2006;107:2013–21.
doi: 10.1182/blood-2005-05-1795
Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T, et al. Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol. 2008;180:7175–83.
doi: 10.4049/jimmunol.180.11.7175
Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D’Acquisto F, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol. 2015;13:e1002202.
doi: 10.1371/journal.pbio.1002202
Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, Ricupito A, et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res. 2012;72:2746–56.
doi: 10.1158/0008-5472.CAN-11-1272
Pearce EL. Metabolism in T cell activation and differentiation. Curr Opin Immunol. 2010;22:314–20.
doi: 10.1016/j.coi.2010.01.018
Siska PJ, Rathmell JC. T cell metabolic fitness in antitumor immunity. Trends Immunol. 2015;36:257–64.
doi: 10.1016/j.it.2015.02.007
MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–83.
doi: 10.1146/annurev-immunol-032712-095956
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4 + T cell subsets. J Immunol. 2011;186:3299–303.
doi: 10.4049/jimmunol.1003613
Murray CM, Hutchinson R, Bantick JR, Belfield GP, Benjamin AD, Brazma D, et al. Monocarboxylate transporter MCT1 is a target for immunosuppression. Nat Chem Biol. 2005;1:371–6.
doi: 10.1038/nchembio744
Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016;24:657–71.
doi: 10.1016/j.cmet.2016.08.011
Eidelman E, Twum-Ampofo J, Ansari J, Siddiqui MM. The metabolic phenotype of prostate cancer. Front Oncol. 2017;7:131.
doi: 10.3389/fonc.2017.00131
Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest. 2013;123:3678–84.
doi: 10.1172/JCI69600
Mishra R, Haldar S, Placencio V, Madhav A, Rohena-Rivera K, Agarwal P, et al. Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming. J Clin Invest. 2018;128:4472–84.
doi: 10.1172/JCI99397
Metzler B, Gfeller P, Guinet E. Restricting glutamine or glutamine-dependent purine and pyrimidine syntheses promotes human T cells with high FOXP3 expression and regulatory properties. J Immunol. 2016;196:3618–30.
doi: 10.4049/jimmunol.1501756
Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al. Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol. 2010;185:1037–44.
doi: 10.4049/jimmunol.0903586
Wang F, Chan CH, Chen K, Guan X, Lin HK, Tong Q. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene. 2012;31:1546–57.
doi: 10.1038/onc.2011.347
Ha TY. The role of regulatory T cells in cancer. Immune Netw. 2009;9:209–35.
doi: 10.4110/in.2009.9.6.209
Flammiger A, Weisbach L, Huland H, Tennstedt P, Simon R, Minner S, et al. High tissue density of FOXP3 + T cells is associated with clinical outcome in prostate cancer. Eur J Cancer. 2013;49:1273–9.
doi: 10.1016/j.ejca.2012.11.035
Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13:39–53.
doi: 10.1111/j.1582-4934.2008.00556.x
Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, et al. Modulation of K-Ras-dependent lung tumorigenesis by microRNA-21. Cancer Cell. 2010;18:282–93.
doi: 10.1016/j.ccr.2010.08.013
Pfeffer SR, Yang CH, Pfeffer LM. The role of miR-21 in cancer. Drug Dev Res. 2015;76:270–7.
doi: 10.1002/ddr.21257
Lim S, Phillips JB, Madeira da Silva L, Zhou M, Fodstad O, Owen LB, et al. Interplay between immune checkpoint proteins and cellular metabolism. Cancer Res. 2017;77:1245–9.
doi: 10.1158/0008-5472.CAN-16-1647
Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162:1229–41.
doi: 10.1016/j.cell.2015.08.016
Hude I, Sasse S, Engert A, Bröckelmann PJ. The emerging role of immune checkpoint inhibition in malignant lymphoma. Haematologica. 2017;102:30–42.
doi: 10.3324/haematol.2016.150656
Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res. 2010;70:6945–56.
doi: 10.1158/0008-5472.CAN-10-0785
Wong N, Yan J, Ojo D, De Melo J, Cutz JC, Tang D. Changes in PKM2 associate with prostate cancer progression. Cancer Invest. 2014;32:330–8.
doi: 10.3109/07357907.2014.919306