CD147‑mediated reprogrammed glycolytic metabolism potentially induces immune escape in the tumor microenvironment (Review)
- Authors:
- Xiaofeng Li
- Wengui Xu
-
Affiliations: Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China - Published online on: March 4, 2019 https://doi.org/10.3892/or.2019.7041
- Pages: 2945-2956
This article is mentioned in:
Abstract
Kareva I and Hahnfeldt P: The emerging ‘hallmarks’ of metabolic reprogramming and immune evasion: Distinct or linked? Cancer Res. 73:2737–2742. 2013. View Article : Google Scholar : PubMed/NCBI | |
Warburg O: On respiratory impairment in cancer cells. Science. 124:269–270. 1956.PubMed/NCBI | |
Li X, Peng J, Pang Y, Yu S, Yu X, Cheng PC, Wang WZ, Han WL, Zhang J, Yin YH and Zhang Y: Identification of a FOXP3+CD3+CD56+ population with immunosuppressive function in cancer tissues of human hepatocellular carcinoma. Sci Rep. 5:147572015. View Article : Google Scholar : PubMed/NCBI | |
Kalathil SG and Thanavala Y: High immunosuppressive burden in cancer patients: A major hurdle for cancer immunotherapy. Cancer Immunol Immunother. 650:813–819. 2016. View Article : Google Scholar | |
Wargo JA, Reddy SM, Reuben A and Sharma P: Monitoring immune responses in the tumor microenvironment. Curr Opin Immunol. 41:23–31. 2016. View Article : Google Scholar : PubMed/NCBI | |
Josefowicz SZ, Lu LF and Rudensky AY: Regulatory T cells: Mechanisms of differentiation and function. Annu Rev Immunol. 30:531–564. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hansen M and Andersen MH: The role of dendritic cells in cancer. Semin Immunopathol. 9:307–316. 2017. View Article : Google Scholar | |
Ni L and Dong C: New checkpoints in cancer immunotherapy. Immunol Rev. 276:52–65. 2017. View Article : Google Scholar : PubMed/NCBI | |
Speiser DE, Ho PC and Verdeil G: Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 16:599–611. 2016. View Article : Google Scholar : PubMed/NCBI | |
Chang CH, Qiu J, O'Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, et al: Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 162:1229–1241. 2015. View Article : Google Scholar : PubMed/NCBI | |
Siska PJ and Rathmell JC: T cell metabolic fitness in antitumor immunity. Trends Immunol. 36:257–264. 2015. View Article : Google Scholar : PubMed/NCBI | |
Gottfried E, Kunz-Schughart LA, Ebner S, Mueller-Klieser W, Hoves S, Andreesen R, Mackensen A and Kreutz M: Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood. 107:2013–2021. 2006. View Article : Google Scholar : PubMed/NCBI | |
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al: Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 109:3812–3819. 2007. View Article : Google Scholar : PubMed/NCBI | |
MacIver NJ, Michalek RD and Rathmell JC: Metabolic regu-lation of T lymphocytes. Annu Rev Immunol. 31:259–283. 2013. View Article : Google Scholar : PubMed/NCBI | |
Gerriets VA and Rathmell JC: Metabolic pathways in T cell fate and function. Trends Immunol. 33:168–173. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chang CH, Curtis JD, Maggi LB Jr, Faubert B, Villarino AV, O'Sullivan D, Huang SC, van der Windt GJ, Blagih J, Qiu J, et al: Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 153:1239–1251. 2013. View Article : Google Scholar : PubMed/NCBI | |
Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, et al: The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 20:61–72. 2014. View Article : Google Scholar : PubMed/NCBI | |
Pearce EL, Poffenberger MC, Chang CH and Jones RG: Fueling immunity: Insights into metabolism and lymphocyte function. Science. 42:12424542013. View Article : Google Scholar | |
Chang CH and Pearce EL: Emerging concepts in immunotherapy-T cell metabolism as a therapeutic target. Nat Immunol. 17:364–368. 2016. View Article : Google Scholar : PubMed/NCBI | |
O'Sullivan D and Pearce EL: Targeting T cell metabolism for therapy. Trends Immunol. 36:71–80. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J, et al: The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 35:871–882. 2011. View Article : Google Scholar : PubMed/NCBI | |
Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR and Chi H: HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 208:1367–1376. 2011. View Article : Google Scholar : PubMed/NCBI | |
So L and Fruman DA: PI3K signalling in B- and T-lymphocytes: New developments and therapeutic advances. Biochem J. 442:465–841. 2012. View Article : Google Scholar : PubMed/NCBI | |
Han JM, Patterson SJ and Levings MK: The role of the PI3K signaling pathway in CD4+ T cell differentiation and function. Front Immunol. 3:2452012. View Article : Google Scholar : PubMed/NCBI | |
Powell JD, Pollizzi KN, Heikamp EB and Horton MR: Regulation of immune responses by mTOR. Annu Rev Immunol. 30:39–68. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chi HB: Regulation and function of mTOR signaling in T cell fate decisions. Nat Rev Immunol. 12:325–338. 2012. View Article : Google Scholar : PubMed/NCBI | |
Weidle UH, Scheuer W, Eggle D, Klostermann S and Stockinger H: Cancer-related issues of CD147. Cancer Genomics Proteomics. 7:157–169. 2010.PubMed/NCBI | |
Riethdorf S, Reimers N, Assmann V, Kornfeld JW, Terracciano L, Sauter G and Pantel K: High incidence of EMMPRIN expression in human tumors. Int J Cancer. 119:1800–1810. 2006. View Article : Google Scholar : PubMed/NCBI | |
Xu J, Xu HY, Zhang Q, Song F, Jiang JL, Yang XM, Mi L, Wen N, Tian R, Wang L, et al: HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma. Mol Cancer Res. 5:605–614. 2007. View Article : Google Scholar : PubMed/NCBI | |
Zhang Q, Zhou J, Ku XM, Chen XG, Zhang L, Xu J, Chen GS, Li Q, Qian F, Tian R, et al: Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma. Eur J Cancer Prev. 16:196–202. 2007. View Article : Google Scholar : PubMed/NCBI | |
Zheng HC, Takahashi H, Murai Y, Cui ZG, Nomoto K, Miwa S, Tsuneyama K and Takano Y: Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: A good marker for local invasion and prognosis. Br J Cancer. 95:1371–1378. 2006. View Article : Google Scholar : PubMed/NCBI | |
Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, Bugelski P and Yan L: Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 65:3193–3199. 2005. View Article : Google Scholar : PubMed/NCBI | |
Tang Y, Nakada MT, Rafferty P, Laraio J, McCabe FL, Millar H, Cunningham M, Snyder LA, Bugelski P and Yan L: Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway. Mol Cancer Res. 4:371–377. 2006. View Article : Google Scholar : PubMed/NCBI | |
Kennedy KM and Dewhirst MW: Tumor metabolism of lactate: The influence and therapeutic potential for MCT and CD147 regulation. Future Oncol. 6:127–148. 2010. View Article : Google Scholar : PubMed/NCBI | |
Halestrap AP and Price NT: The proton-linked monocarboxylate transporter (MCT) family: Structure, function and regulation. Biochem J. 343:281–299. 1999. View Article : Google Scholar : PubMed/NCBI | |
Halestrap AP and Wilson MC: The monocarboxylate transporter family-role and regulation. IUBMB Life. 64:109–119. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN and Halestrap AP: CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 19:3896–3904. 2000. View Article : Google Scholar : PubMed/NCBI | |
Li XF, Yu XZ, Song XY, Dai D and Xu WG: The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters. Oncotarget. 7:23141–23155. 2016.PubMed/NCBI | |
Kroemer G and Pouyssegur J: Tumor Cell Metabolism: Cancer's Achilles' Heel. Cancer Cell. 13:472–482. 2008. View Article : Google Scholar : PubMed/NCBI | |
Hsu PP and Sabatini DM: Cancer cell metabolism: Warburg and beyond. Cell. 134:703–707. 2014. View Article : Google Scholar | |
Levine AJ and Puzio-Kuter AM: The control of the metabolic switch in cancers by oncogenes and tumor suppressors genes. Science. 330:1340–1344. 2010. View Article : Google Scholar : PubMed/NCBI | |
Tennant DA, Duran RV and Gottlieb E: Targeting metabolic transformation for cancer therapy. Nat Rev Cancer. 10:267–277. 2010. View Article : Google Scholar : PubMed/NCBI | |
Madan E, Gogna R, Bhatt M, Pati U, Kuppusamy P and Mahdi AA: Regulation of glucose metabolism by p53: Emerging new roles for the tumor suppressor. Oncotarget. 2:948–957. 2011. View Article : Google Scholar : PubMed/NCBI | |
Zhang C, Liu J, Wu R, Liang Y, Lin M, Liu J, Chan CS, Hu W and Feng Z: Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia through its target RRAD. Oncotarget. 5:5535–5546. 2014. View Article : Google Scholar : PubMed/NCBI | |
Schwartzenberg-Bar-Yoseph F, Armoni M and Karnieli E: The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 64:2627–2633. 2004. View Article : Google Scholar : PubMed/NCBI | |
Dang CV, Le A and Gao P: MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res. 15:6479–6483. 2009. View Article : Google Scholar : PubMed/NCBI | |
Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R and Dang CV: c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth. Proc Natl Acad Sci USA. 94:6658–6663. 1997. View Article : Google Scholar : PubMed/NCBI | |
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG and Rathmell JC: Cutting Edge: Distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 186:3299–3303. 2011. View Article : Google Scholar : PubMed/NCBI | |
Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA and Dang CV: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 275:21797–21800. 2000. View Article : Google Scholar : PubMed/NCBI | |
Kim JW, Gao P, Liu YC, Semenza GL and Dang CV: Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol. 27:7381–7393. 2007. View Article : Google Scholar : PubMed/NCBI | |
Dang CV, Kim JW, Gao P and Yustein J: The interplay between MYC and HIF in cancer. Nat Rev Cancer. 8:51–56. 2008. View Article : Google Scholar : PubMed/NCBI | |
Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3:177–185. 2006. View Article : Google Scholar : PubMed/NCBI | |
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM and Thompson CB: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64:3892–3899. 2004. View Article : Google Scholar : PubMed/NCBI | |
Makinoshima H, Takita M, Saruwatari K, Umemura S, Obata Y, Ishii G, Matsumoto S, Sugiyama E, Ochiai A, Abe R, et al: Signaling through the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) axis is responsible for aerobic glycolysis mediated by glucose transporter in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. J Biol Chem. 290:17495–17504. 2015. View Article : Google Scholar : PubMed/NCBI | |
Laplante M and Sabatini DM: mTOR signaling at a glance. J Cell Sci. 122:3589–3594. 2009. View Article : Google Scholar : PubMed/NCBI | |
Woo YM, Shin Y, Lee EJ, Lee S, Jeong SH, Kong HK, Park EY, Kim HK, Han J, Chang M, et al: Inhibition of aerobic glycolysis represses Akt/mTOR/HIF-1α axis and restores tamoxifen sensitivity in antiestrogen-resistant breast cancer cells. PLoS One. 10:e01322852015. View Article : Google Scholar : PubMed/NCBI | |
Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, et al: mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 345:12506842014. View Article : Google Scholar : PubMed/NCBI | |
Denko NC: Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 8:705–713. 2008. View Article : Google Scholar : PubMed/NCBI | |
Lu H, Forbes RA and Verma A: Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 277:23111–23115. 2002. View Article : Google Scholar : PubMed/NCBI | |
Liu J, Zhang C, Hu WW and Feng ZH: Tumor suppressor p53 and its mutants in cancer metabolism. Cancer Lett. 356:197–203. 2015. View Article : Google Scholar : PubMed/NCBI | |
Vousden KH and Ryan KM: p53 and metabolism. Nat Rev Cancer. 9:691–700. 2009. View Article : Google Scholar : PubMed/NCBI | |
Yeung SJ, Pan J and Lee MH: Roles of p53, MYC and HIF-1 in regulating glycolysis-the seventh hallmark of cancer. Cell Mol Life Sci. 65:3981–3999. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, Masuyama N and Gotoh Y: Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem. 277:21843–21850. 2002. View Article : Google Scholar : PubMed/NCBI | |
Warburg O, Gawehn K and Geissler AW: Metabolism of leukocytes. Z Naturforsch B. 13B:515–516. 1958.(In German). View Article : Google Scholar : PubMed/NCBI | |
Jacobs SR, Michalek RD and Rathmell JC: IL-7 is essential for homeostatic control of T cell metabolism in vivo. J Immunol. 184:3461–3469. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wang R and Green DR: Metabolic checkpoints in activated T cells. Nat Immunol. 13:907–915. 2012. View Article : Google Scholar : PubMed/NCBI | |
Vander-Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI | |
Van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ and Pearce EL: Mitichondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 36:68–78. 2012. View Article : Google Scholar : PubMed/NCBI | |
van der Windt GJ, O'Sullivan D, Everts B, Huang SC, Buck MD, Curtis JD, Chang CH, Smith AM, Ai T, Faubert B, et al: CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability. Proc Natl Acad Sci USA. 110:14336–14341. 2013. View Article : Google Scholar : PubMed/NCBI | |
Mannava S, Grachtchouk V, Wheeler LJ, Im M, Zhuang D, Slavina EG, Mathews CK, Shewach DS and Nikiforov MA: Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle. 7:2392–2400. 2008. View Article : Google Scholar : PubMed/NCBI | |
Shen Y, Wei Y, Wang Z, Jing Y, He H, Yuan J, Li R, Zhao Q, Wei L, Yang T, et al: TGF-β regulates hepatocellular carcinoma progression by inducing Treg cell polarization. Cell Physiol Biochem. 35:1623–1632. 2015. View Article : Google Scholar : PubMed/NCBI | |
Kalathil S, Lugade AA, Miller A, Iyer R and Thanavala Y: Higher frequencies of GARP+CTLA-4+Foxp3+ T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality. Cancer Res. 73:2435–2444. 2013. View Article : Google Scholar : PubMed/NCBI | |
Galgani M, De Rosa V, La Cava A and Matarese G: Role of metabolism in the immunobiology of regulatory T cells. J Immunol. 197:2567–2575. 2016. View Article : Google Scholar : PubMed/NCBI | |
Procaccini C, Carbone F, Di Silvestre D, Brambilla F, De Rosa V, Galgani M, Faicchia D, Marone G, Tramontano D, Corona M, et al: The protemic landscape of human ex vivo regulatory and conventional T cells reveals specific metabolic requirements. Immunity. 44:406–421. 2016. View Article : Google Scholar : PubMed/NCBI | |
Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, et al: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 458:762–765. 2009. View Article : Google Scholar : PubMed/NCBI | |
Cham CM, Driessens G, O'Keefe JP and Gajewski TF: Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. J Immunol. 38:2438–2450. 2008. | |
Siska PJ, van der Windt GJ, Kishton RJ, Cohen S, Eisner W, MacIver NJ, Kater AP, Weinberg JB and Rathmell JC: Suppression of Glut1 and glucose metabolism by decreased Akt/mTORC1 signaling drives T cell impairment in B cell leukemia. J Immunol. 197:2532–2540. 2016. View Article : Google Scholar : PubMed/NCBI | |
Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, et al: Control of TH17/Treg balance by hypoxia-inducible factor 1. Cell. 146:772–784. 2011. View Article : Google Scholar : PubMed/NCBI | |
Chen L and Flies DB: Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 3:227–242. 2013. View Article : Google Scholar | |
Wieman HL, Wofford JA and Rathmell JC: Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell. 18:1437–1446. 2007. View Article : Google Scholar : PubMed/NCBI | |
Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, Worley PF, Kozma SC and Powell JD: The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity. 30:832–844. 2009. View Article : Google Scholar : PubMed/NCBI | |
Liu C, Chapman NM, Karmaus PW, Zeng H and Chi H: mTOR and metabolic regulation of conventional and regulatory T cells. J Leukoc Biol. 7:837–847. 2015. View Article : Google Scholar | |
Procaccini C, De Rosa V, Galgani M, Abanni L, Calì G, Porcellini A, Carbone F, Fontana S, Horvath TL, La Cava A, et al: An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity. 33:929–941. 2010. View Article : Google Scholar : PubMed/NCBI | |
Mihaylova MM and Shaw RJ: The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol. 13:1016–1023. 2011. View Article : Google Scholar : PubMed/NCBI | |
Blagih J, Coulombe F, Vincent EE, Dupuy F, Galicia-Vázquez G, Yurchenko E, Raissi TC, van der Windt GJ, Viollet B, Pearce EL, et al: The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity. 42:41–54. 2015. View Article : Google Scholar : PubMed/NCBI | |
Dunn GP, Bruce AT, Ikeda H, Old LJ and Schreiber RD: Cancer immunoediting: From immunosurveilance to tumor escape. Nat Immunol. 3:991–998. 2002. View Article : Google Scholar : PubMed/NCBI | |
Liu Y and Cao XT: Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med. 94:509–522. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wang TT, Liu GW and Wang RN: The intercellular metabolic interplay between tumor and immune cells. Front Immunol. 5:3582014. View Article : Google Scholar : PubMed/NCBI | |
Slomiany MG, Grass GD, Robertson AD, Yang XY, Maria BL, Beeson C and Toole BP: Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res. 69:1293–1301. 2009. View Article : Google Scholar : PubMed/NCBI | |
Hirschhaeuser F, Sattler UG and Mueller-Klieser W: Lactate: A metabolic key player in cancer. Cancer Res. 71:6921–6925. 2011. View Article : Google Scholar : PubMed/NCBI | |
Le Floch R, Chiche J, Marchiq I, Naiken T, Ilc K, Murray CM, Critchlow SE, Roux D, Simon MP and Pouysségur J: CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc Natl Acad Sci USA. 108:16663–16668. 2011. View Article : Google Scholar : PubMed/NCBI | |
Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, Wang C, Flomenberg N, Knudsen ES, Howell A, et al: Ketones and lactate increase cancer cell ‘stemness,’ driving recurrence, metastasis and poor clinical outcome in breast cancer: Achieving personalized medicine via Metabolo-Genomics. Cell Cycle. 10:1271–1286. 2011. View Article : Google Scholar : PubMed/NCBI | |
Goetze K, Walenta S, Ksiazkiewicz M, Kunz-Schughart LA and Mueller-Klieser W: Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int J Oncol. 39:453–463. 2011.PubMed/NCBI | |
Wong TY, Phillips AO, Witowski J and Topley N: Glucose-mediated induction of TGF-β1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent. Kidney Int. 63:1404–1416. 2003. View Article : Google Scholar : PubMed/NCBI | |
Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, Honnons S, Jones C, Isern NG, Hu JZ, et al: Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β. Am J Respir Crit Care Med. 186:740–751. 2012. View Article : Google Scholar : PubMed/NCBI | |
Rudrabhatla SR, Mahaffey CL and Mummert ME: Tumor microenvironment modulates hyaluronan expression: The lactate effect. J Invest Dermatol. 126:1378–1387. 2006. View Article : Google Scholar : PubMed/NCBI | |
Gottfried E, Kreutz M and Mackensen A: tumor metabolism as modulator of immune response and tumor progression. Semin Cancer Biol. 22:335–341. 2012. View Article : Google Scholar : PubMed/NCBI | |
Husain Z, Huang Y, Seth P and Sukhatme VP: Tumor-derived lactate modifies antitumor immune response: Effect on myeloid-derived suppressor cells and NK cells. J Immunol. 191:1486–1495. 2013. View Article : Google Scholar : PubMed/NCBI | |
Feder-Mengus C, Ghosh S, Weber WP, Wyler S, Zajac P, Terracciano L, Oertli D, Heberer M, Martin I, Spagnoli GC, et al: Multiple mechanisms underlie defective recognition of melanoma cells cultured in three-dimensional architectures by antigen-specific cytotoxic T lymphocytes. Br J Cancer. 96:1072–1082. 2007. View Article : Google Scholar : PubMed/NCBI | |
Mendler AN, Hu B, Prinz PU, Kreutz M, Gottfried E and Noessner E: Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun activation. Int J Cancer. 131:633–640. 2012. View Article : Google Scholar : PubMed/NCBI | |
Gatenby RA, Gawlinski ET, Gmitro AF, Kaylor B and Gillies RJ: Acid-mediated tumor invasion: A multidisciplinary study. Cancer Res. 66:5216–5223. 2006. View Article : Google Scholar : PubMed/NCBI | |
McCarty MF and Whitaker J: Manipulating tumor acidification as a cancer treatment strategy. Altern Med Rev. 15:264–272. 2010.PubMed/NCBI | |
Hu XY and Ivashkiv LB: Cross-regulation of signaling pathways by interferon-gamma: Implications for immune responses and autoimmune diseases. Immunity. 31:539–550. 2009. View Article : Google Scholar : PubMed/NCBI | |
Nathan I, Groopman JE, Quan SG, Bersch N and Golde DW: Immune (gamma) interferon produced by a human T-lymphoblast cell line. Nature. 292:842–844. 1981. View Article : Google Scholar : PubMed/NCBI | |
Mekhail K, Gunaratnam L, Bonicalzi ME and Lee S: HIF activation by pH-dependent nucleolar sequestration of VHL. Nat Cell Biol. 6:642–647. 2004. View Article : Google Scholar : PubMed/NCBI | |
McMahon S, Charbonneau M, Grandmont S, Richard DE and Dubois CM: Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem. 281:24171–24181. 2006. View Article : Google Scholar : PubMed/NCBI | |
Clambey ET, McNamee EN, Westrich JA, Glover LE, Campbell EL, Jedlicka P, de Zoeten EF, Cambier JC, Stenmark KR, Colgan SP, et al: 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 USA. 109:E2784–E2793. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hung SP, Yang MH, Tseng KF and Lee OK: Hypoxia-induced secretion of TGF-β1 in mesenchymal stem cell promotes breast cancer cell progression. Cell Transplant. 22:1869–1882. 2013. View Article : Google Scholar : PubMed/NCBI | |
Sanjabi S, Oh SA and Li MO: Regulation of the immune response by TGF-β: From conception to autoimmunity and infection. Cold Spring Harb Perspect Biol. 9(pii): a0222362017. View Article : Google Scholar : PubMed/NCBI | |
Barsoum IB, Smallwood CA, Siemens DR and Graham CH: A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 74:665–674. 2014. View Article : Google Scholar : PubMed/NCBI | |
Park BV, Freeman ZT, Ghasemzadeh A, Chattergoon MA, Rutebemberwa A, Steigner J, Winter ME, Huynh TV, Sebald SM, Lee SJ, et al: TGF-β1-mediated SMAD3 enhances PD-1 expression on antigen-specific T Cells in cancer. Cancer Discov. 6:1366–1381. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wei S, Shreiner AB, Takeshita N, Chen L, Zou W and Chang AE: Tumor-induced immune suppression of in vivo effector T-cell priming is mediated by the B7-H1/PD-1 axis and transforming growth factor beta. Cancer Res. 68:5432–5438. 2008. View Article : Google Scholar : PubMed/NCBI | |
Mamori S, Nagatsuma K, Matsuura T, Ohkawa K, Hano H, Fukunaga M, Matsushima M, Masui Y, Fushiya N, Onoda H, et al: Useful detection of CD147 (EMMPRIN) for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples. World J Gastroenterol. 13:2913–2917. 2007. View Article : Google Scholar : PubMed/NCBI | |
Tang J, Wu YM, Zhao P, Yang XM, Jiang JL and Chen ZN: Overexpression of HAb18G/CD147 promotes invasion an metastasis via alpha3beta1 integrin mediated FAK-paxilli and FAK-PI3K-Ca2+ pathways. Cell Mol Life Sci. 65:2933–2942. 2008. View Article : Google Scholar : PubMed/NCBI | |
Dai JY, Dou KF, Wang CH, Zhao P, Lau WB, Tao L, Wu YM, Tang J, Jiang JL and Chen ZN: The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells. BMC Cancer. 9:337–346. 2009. View Article : Google Scholar : PubMed/NCBI | |
Zhao P, Zhang W, Tang J, Ma XK, Dai JY, Li Y, Jiang JL, Zhang SH and Chen ZN: Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. Cancer Sci. 101:387–395. 2010. View Article : Google Scholar : PubMed/NCBI | |
Baba M, Inoue M, Itoh K and Nishizawa Y: Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism. Biochem Biophys Res Commun. 374:111–116. 2008. View Article : Google Scholar : PubMed/NCBI | |
Su J, Chen X and Kanekura TA: CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis. Cancer Lett. 273:140–147. 2009. View Article : Google Scholar : PubMed/NCBI | |
Huang QC, Li JB, Xing JL, Li WW, Li HW, Ke X, Zhang J, Ren TT, Shang YK, Yang HS, et al: CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway. J Hepatol. 61:859–866. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ke X, Fei F, Chen YK, Xu L, Zhang Z, Huang QC, Zhang HX, Yang HS, Chen ZN and Xing JL: Hypoxia upregulates CD147 through a combined effect of HIF-1alpha and Sp1 to promote glycolysis and tumor progression in epithelial solid tumors. Carcinogenesis. 33:1598–1607. 2012. View Article : Google Scholar : PubMed/NCBI | |
Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, et al: Hepatitis B virus X protein shifts human hepatic transforming factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hetatitis B. Hepatology. 49:1203–1217. 2009. View Article : Google Scholar : PubMed/NCBI | |
Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI | |
Xu J, Lamouille S and Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 19:156–172. 2009. View Article : Google Scholar : PubMed/NCBI | |
Wu J, Ru NY, Zhang Y, Li Y, Wei D, Ren Z, Huang XF, Chen ZN and Bian H: HAb18G/CD147 promotes epithelial-mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug. Oncogene. 30:4410–4427. 2011. View Article : Google Scholar : PubMed/NCBI | |
Wang GL, Jiang BH, Rue EA and Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 92:5510–5514. 1995. View Article : Google Scholar : PubMed/NCBI | |
Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL and Cantley LC: The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 52:230–233. 2008. View Article : Google Scholar | |
Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL and Chen ZN: Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma. J Cell Mol Med. 15:1415–1428. 2011. View Article : Google Scholar : PubMed/NCBI | |
Guo H, Majmudar G, Jensen TC, Biswas C, Toole BP and Gordon MK: Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of matrix metalloproteinases. Gene. 220:99–108. 1998. View Article : Google Scholar : PubMed/NCBI | |
Yang H, Zou W and Chen BL: Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment. Cell Biol Int. 37:1139–1142. 2013. View Article : Google Scholar : PubMed/NCBI | |
Kong LM, Liao CG, Fei F, Guo X, Xing JL and Chen ZN: Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci. 101:1463–1470. 2010. View Article : Google Scholar : PubMed/NCBI | |
Kono K: Current status of cancer immunotherapy. J Stem Cells Regen Med. 10:8–13. 2014.PubMed/NCBI | |
Sangro B, Gomez-Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, Riezu-Boj JI, Larrea E, Alfaro C, Sarobe P, et al: A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol. 59:81–88. 2013. View Article : Google Scholar : PubMed/NCBI | |
Prat A, Navarro A, Paré L, Reguart N, Galván P, Pascual T, Martínez A, Nuciforo P, Comerma L, Alos L, et al: Immune-related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma, head and neck squamous cell carcinoma and melanoma. Cancer Res. 77:3540–3550. 2017. View Article : Google Scholar : PubMed/NCBI | |
Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, Lantz O, Romano E, Milder M, Buecher B, et al: Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: A proof-of-concept study. Ann Oncol. 28:1996–2001. 2017. View Article : Google Scholar : PubMed/NCBI | |
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, et al: PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 6:66922015. View Article : Google Scholar : PubMed/NCBI | |
Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, Bronte V and Chouaib S: PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 211:781–790. 2014. View Article : Google Scholar : PubMed/NCBI | |
Kizaka-Kondoh S, Tanaka S, Harada H and Hiraoka M: The HIF-1-active microenvironment: An environmental target for cancer therapy. Adv Drug Deliv Rev. 61:623–632. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li B and Simon MC: Molecular pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer. Clin Cancer Res. 19:5835–5841. 2013. View Article : Google Scholar : PubMed/NCBI | |
Okkenhaug K, Graupera M and Vanhaesebroeck B: Targeting PI3K in cancer: Impact on tumor cells, their protective stroma, angiogenesis, and immunotherapy. Cancer Discov. 6:1090–1105. 2016. View Article : Google Scholar : PubMed/NCBI | |
Thorpe LM, Yuzugullu H and Zhao JJ: PI3K in cancer: Divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 15:7–24. 2015. View Article : Google Scholar : PubMed/NCBI | |
Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI | |
Troncone M, Cargnelli SM, Villani LA, Isfahanian N, Broadfield LA, Zychla L, Wright J, Pond G, Steinberg GR and Tsakiridis T: Targeting metabolism and AMP-activated kinase with metformin to sensitize non-small cell lung cancer (NSCLC) to cytotoxic therapy; translational biology and rationale for current clinical trials. Oncotarget. 8:57733–57754. 2017. View Article : Google Scholar : PubMed/NCBI | |
Luchsinger JA, Ma Y, Christophi CA, Florez H, Golden SH, Hazuda H, Crandall J, Venditti E, Watson K, Jeffries S, et al: Diabetes Prevention Program Research Group: Metformin, lifestyle intervention, and cognition in the diabetes prevention program outcomes study. Diabetes Care. 40:958–965. 2017. View Article : Google Scholar : PubMed/NCBI | |
Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, et al: Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol. 40:685–693. 2005. View Article : Google Scholar : PubMed/NCBI | |
Dowling RJ, Zakikhani M, Fantus IG, Pollak M and Sonenberg N: Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 67:10804–10812. 2007. View Article : Google Scholar : PubMed/NCBI | |
Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD and Evans JM: New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care. 32:1620–1625. 2009. View Article : Google Scholar : PubMed/NCBI | |
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN and Gonzalez-Angulo AM: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 27:3297–3302. 2009. View Article : Google Scholar : PubMed/NCBI | |
Christofk HR, Vander Heiden MG, Wu N, Asara JM and Cantley LC: Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 452:181–186. 2008. View Article : Google Scholar : PubMed/NCBI | |
Bian H, Zheng JS, Nan G, Li R, Chen C, Hu CX, Zhang Y, Sun B, Wang XL, Cui SC, et al: Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation. J Natl Cancer Inst. 106(pii): dju2392014.PubMed/NCBI | |
Calvaresi EC and Hergenrother PJ: Glucose conjugation for the specific targeting and treatment of cancer. Chem Sci. 4:2319–2333. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ciuleanu TE, Pavlovsky AV, Bodoky G, Garin AM, Langmuir VK, Kroll S and Tidmarsh GT: A randomised Phase III trial of glufosfamide compared with best supportive care in metastatic pancreatic adenocarcinoma previously treated with gemcitabine. Eur J Cancer. 45:1589–1596. 2009. View Article : Google Scholar : PubMed/NCBI | |
Baeuerle PA and Reinhardt C: Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 69:4941–4944. 2009. View Article : Google Scholar : PubMed/NCBI | |
Lameris R, de Bruin RC, Schneiders FL, van Bergen en Henegouwen PM, Verheul HM, de Gruijl TD and van der Vliet HJ: Bispecific antibody platforms for cancer immunotherapy. Crit Rev Oncol Hematol. 92:153–165. 2014. View Article : Google Scholar : PubMed/NCBI | |
Smith DM, Simon JK and Baker JR Jr: Applications of nanotechnology for immunology. Nat Rev Immunol. 13:592–605. 2013. View Article : Google Scholar : PubMed/NCBI | |
Metcalfe SM and Fahmy TM: Targeted nanotherapy for induction of therapeutic immune responses. Trends Mol Med. 18:72–80. 2012. View Article : Google Scholar : PubMed/NCBI |