Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Review

Effects of tumor metabolic microenvironment on regulatory T cells

Authors: Yi-an Wang, Xiao-Ling Li, Yong-Zhen Mo, Chun-Mei Fan, Le Tang, Fang Xiong, Can Guo, Bo Xiang, Ming Zhou, Jian Ma, Xi Huang, Xu Wu, Yong Li, Gui-Yuan Li, Zhao-yang Zeng, Wei Xiong

Published in: Molecular Cancer | Issue 1/2018

Login to get access

Abstract

Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body’s immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy.
Literature
1.
Wei F, Wu Y, Tang L, Xiong F, Guo C, Li X, Zhou M, Xiang B, Li X, Li G, et al. Trend analysis of cancer incidence and mortality in China. Sci China Life Sci. 2017;60(11):1271–5.PubMedCrossRef
2.
3.
Tu C, Zeng Z, Qi P, Li X, Guo C, Xiong F, Xiang B, Zhou M, Liao Q, Yu J, et al. Identification of genomic alterations in nasopharyngeal carcinoma and nasopharyngeal carcinoma-derived Epstein-Barr virus by whole genome sequencing. Carcinogenesis. 2018; https://​doi.​org/​10.​1093/​carcin/​bgy108.
4.
Zou G, Ren B, Liu Y, Fu Y, Chen P, Li X, Luo S, He J, Gao G, Zeng Z, et al. INHBB suppresses anoikis resistance and migration through TGF-beta signaling pathway in nasopharyngeal carcinoma. Cancer Sci. 2018;109(11):3416–27.PubMedPubMedCentralCrossRef
5.
Tang Y, He Y, Zhang P, Wang J, Fan C, Yang L, Xiong F, Zhang S, Gong Z, Nie S, et al. LncRNAs regulate the cytoskeleton and related rho/ROCK signaling in cancer metastasis. Mol Cancer. 2018;17(1):77.
6.
Wei F, Tang L, He Y, Wu Y, Shi L, Xiong F, Gong Z, Guo C, Li X, Liao Q, et al. BPIFB1 (LPLUNC1) inhibits radioresistance in nasopharyngeal carcinoma by inhibiting VTN expression. Cell Death Dis. 2018;9(4):432.
7.
Yang L, Tang Y, Xiong F, He Y, Wei F, Zhang S, Guo C, Xiang B, Zhou M, Xie N, et al. LncRNAs regulate cancer metastasis via binding to functional proteins. Oncotarget. 2017;9(1):1426–43.
8.
Wei F, Wu Y, Tang L, He Y, Shi L, Xiong F, Gong Z, Guo C, Li X, Liao Q, et al. BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM. Br J Cancer. 2018;118(2):233–47.PubMedPubMedCentralCrossRef
9.
Tang Y, Wang J, Lian Y, Fan C, Zhang P, Wu Y, Li X, Xiong F, Li X, Li G, et al. Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Mol Cancer. 2017;16(1):42.
10.
He B, Li W, Wu Y, Wei F, Gong Z, Bo H, Wang Y, Li X, Xiang B, Guo C, et al. Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell metastasis and invasion by targeting long non-coding RNA LOC553103. Cell Death Dis. 2016;7(9):e2353.CrossRef
11.
Zhong Y, Du Y, Yang X, Mo Y, Fan C, Xiong F, Ren D, Ye X, Li C, Wang Y, et al. Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer. 2018;17(1):79.
12.
Zhou R, Wu Y, Wang W, Su W, Liu Y, Wang Y, Fan C, Li X, Li G, Li Y, et al. Circular RNAs (circRNAs) in cancer. Cancer Lett. 2018;425:134–42.PubMedCrossRef
13.
Yu J, Liu Y, Gong Z, Zhang S, Guo C, Li X, Tang Y, Yang L, He Y, Wei F, et al. Overexpression long non-coding RNA LINC00673 is associated with poor prognosis and promotes invasion and metastasis in tongue squamous cell carcinoma. Oncotarget. 2017;8(10):16621–32.
14.
Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, Gong Z, Zhang S, Zhou J, Cao K, et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017;8(5):761–73.PubMedPubMedCentralCrossRef
15.
Chen S, Zheng P, Wang W, Yi M, Chen P, Cai J, Li J, Peng Q, Ban Y, Zhou Y, et al. Abberent expression of NOR1 protein in tumor associated macrophages contributes to the development of DEN-induced hepatocellular carcinoma. J Cell Physiol. 2018;233(6):5002–13.PubMedCrossRef
16.
Fan C, Tang Y, Wang J, Xiong F, Guo C, Wang Y, Xiang B, Zhou M, Li X, Wu X, et al. The emerging role of Epstein-Barr virus encoded microRNAs in nasopharyngeal carcinoma. J Cancer. 2018;9(16):2852–64.PubMedPubMedCentralCrossRef
17.
Yi M, Cai J, Li J, Chen S, Zeng Z, Peng Q, Ban Y, Zhou Y, Li X, Xiong W, et al. Rediscovery of NF-kappaB signaling in nasopharyngeal carcinoma: how genetic defects of NF-kappaB pathway interplay with EBV in driving oncogenesis? J Cell Physiol. 2018;233(8):5537–49.PubMedCrossRef
18.
Tang Y, He Y, Shi L, Yang L, Wang J, Lian Y, Fan C, Zhang P, Guo C, Zhang S, et al. Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma. Oncotarget. 2017;8(24):39001–11.
19.
Wang JP, Tang YY, Fan CM, Guo C, Zhou YH, Li Z, Li XL, Li Y, Li GY, Xiong W, et al. The role of exosomal non-coding RNAs in cancer metastasis. Oncotarget. 2017;9(15):12487–502.
20.
Tang L, Wei F, Wu Y, He Y, Shi L, Xiong F, Gong Z, Guo C, Li X, Deng H, et al. Role of metabolism in cancer cell radioresistance and radiosensitization methods. J Exp Clin Cancer Res. 2018;37(1):87.
21.
Wang W, Yi M, Zhang R, Li J, Chen S, Cai J, Zeng Z, Li X, Xiong W, Wang L, et al. Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma. Mol Cell Biochem. 2018;438(1–2):47–57.PubMedCrossRef
22.
Zhang Y, Xia M, Jin K, Wang S, Wei H, Fan C, Wu Y, Li X, Li X, Li G, et al. Function of the c-met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol Cancer. 2018;17(1):45.
23.
Tu C, Zeng Z, Qi P, Li X, Yu Z, Guo C, Xiong F, Xiang B, Zhou M, Gong Z, et al. Genome-Wide Analysis of 18 Epstein-Barr Viruses Isolated from Primary Nasopharyngeal Carcinoma Biopsy Specimens. J Virol. 2017;91(17):e00301–17.
24.
Folkman J. Fundamental concepts of the angiogenic process. Current Molecular Medicine. 2003;3(7):643–51.PubMedCrossRef
25.
Kim Y, Nam HJ, Lee J, Park DY, Kim C, Yu YS, Kim D, Park SW, Bhin J, Hwang D, et al. Methylation-dependent regulation of HIF-1alpha stability restricts retinal and tumour angiogenesis. Nat Commun. 2016;7:10347.
26.
Hida K, Maishi N, Torii C, Hida Y. Tumor angiogenesis--characteristics of tumor endothelial cells. Int J Clin Oncol. 2016;21(2):206–12.PubMedCrossRef
27.
Warburg O, Wind F, Negelein E. The Metabolism of Tumors in the Body. J Gen Physiol. 1926;8(6):519–30.
28.
Yi M, Li J, Chen S, Cai J, Ban Y, Peng Q, Zhou Y, Zeng Z, Peng S, Li X, et al. Emerging role of lipid metabolism alterations in Cancer stem cells. J Exp Clin Cancer Res. 2018;37(1):118.
29.
Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S, Moreno-Sánchez R. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 2009;9(9):1084–101.
30.
Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV. C-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA. 1997;94(13):6658–63.CrossRef
31.
Baltazar F, Pinheiro C, Morais-Santos F, Azevedo-Silva J, Queirós O, Preto A, Casal M. Monocarboxylate transporters as targets and mediators in cancer therapy response. Histol Histopathol. 2014;29(12):1511–24.
32.
Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman D, et al. Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res. 2011;71(9):3364–76.PubMedCrossRef
33.
Stock C, Cardone RA, Busco G, Krähling H, Schwab A, Reshkin SJ. Protons extruded by NHE1: digestive or glue? Eur J Cell Biol. 2008;87(8–9):591–9.PubMedCrossRef
34.
Hilvo M, Orešič AM. Regulation of lipid metabolism in breast cancer provides diagnostic and therapeutic opportunities. Clin Lipidol. 2012;7(2):177–88.CrossRef
35.
Schulze A, Harris AL. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature. 2012;491(7424):364–73.PubMedCrossRef
36.
Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013;496(7443):101–5.PubMedPubMedCentralCrossRef
37.
38.
Payen VL, Porporato PE, Baselet B, Sonveaux P. Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway. Cell Mol Life Sci. 2016;73(7):1333–48.PubMedCrossRef
39.
Porporato PE, Payen VL, Baselet B, Sonveaux P. Metabolic changes associated with tumor metastasis, part 2: mitochondria, lipid and amino acid metabolism. Cell Mol Life Sci. 2016;73(7):1349–63.PubMedCrossRef
40.
He R, Liu P, Xie X, Zhou Y, Liao Q, Xiong W, Li X, Li G, Zeng Z, Tang H. circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a. J Exp Clin Cancer Res. 2017;36(1):145.
41.
Fan C, Tang Y, Wang J, Xiong F, Guo C, Wang Y, Zhang S, Gong Z, Wei F, Yang L, et al. Role of long non-coding RNAs in glucose metabolism in cancer. Mol Cancer. 2017;16(1):130.
42.
Li Q, Chen P, Zeng Z, Liang F, Song Y, Xiong F, Li X, Gong Z, Zhou M, Xiang B, et al. Yeast two-hybrid screening identified WDR77 as a novel interacting partner of TSC22D2. Tumour Biol. 2016;37(9):12503–12.PubMedCrossRef
43.
Liang F, Li Q, Li X, Li Z, Gong Z, Deng H, Xiang B, Zhou M, Li X, Li G, et al. TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. Int J Oncol. 2016;49(3):1046–56.PubMedCrossRef
44.
He Y, Jing Y, Wei F, Tang Y, Yang L, Luo J, Yang P, Ni Q, Pang J, Liao Q, et al. Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma. Cell Death Dis. 2018;9(2):235.
45.
Martin Villalba MGR, Lopez-Royuela N, Krzywinska E, Garaude J, Allende-Vega N. From tumor cell metabolism to tumor immune escape. International Journal of Biochemistry & Cell Biology. 2013;45(1):106–13.CrossRef
46.
Bhatia A, Kumar Y. Cellular and molecular mechanisms in cancer immune escape: a comprehensive review. Expert Rev Clin Immunol. 2014;10(1):41–62.PubMedCrossRef
47.
48.
49.
Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179.
50.
Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, Fu YX. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med. 2005;201(5):779–91.PubMedPubMedCentralCrossRef
51.
Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, Zhou G, Rajapaksa R, Green MR, Torchia J, Brody J, et al. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 2013;123(6):2447–63.PubMedCrossRefPubMedCentral
52.
Shimizu J, Yamazaki S, Sakaguchi S. Induction of Tumor Immunity by Removing CD251CD41 T Cells A Common Basis Between Tumor Immunity and Autoimmunity. J Immunol. 1999;163(10):5211–8.
53.
Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor Rejection by in Vivo Administration of Anti-CD25 (Interleukin-2 Receptor α) Monoclonal Antibody. Cancer Res. 1999;59(13):3128–33.
54.
Yoshie O, Matsushima K. CCR4 and its ligands: from bench to bedside. Int Immunol. 2015;27(1):11–20.PubMedCrossRef
55.
Yamazaki S, Iyoda T, Tarbell K, Olson K, Velinzon K, Inaba K, Steinman RM. Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J Exp Med. 2003;198(2):235–47.PubMedPubMedCentralCrossRef
56.
Qiu B, Zhang D, Wang C, Tao J, Tie X, Qiao Y, Xu K, Wang Y, Wu A. IL-10 and TGF-beta2 are overexpressed in tumor spheres cultured from human gliomas. Mol Biol Rep. 2011;38(5):3585–91.
57.
Chen J, Ye Y, Liu P, Yu W, Wei F, Li H, Yu J. Suppression of T cells by myeloid-derived suppressor cells in cancer. Hum Immunol. 2017;78(2):113–9.
58.
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;115(3):1151–64.
59.
Curotto de Lafaille MA, Lafaille JJ. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity. 2009;30(5):626–35.PubMedCrossRef
60.
Lourenco EV, La Cava A. Natural regulatory T cells in autoimmunity. Autoimmunity. 2011;44(1):33–42.PubMedCrossRef
61.
Li B, Greene MI. Special regulatory T-cell review: FOXP3 biochemistry in regulatory T cells--how diverse signals regulate suppression. Immunology. 2008;123(1):17–9.PubMedPubMedCentralCrossRef
62.
Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330–6.PubMedCrossRef
63.
Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nagao-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, et al. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proc Natl Acad Sci USA. 2014;111(14):5289–94.
64.
65.
van der Veeken J, Arvey A, Rudensky A. Transcriptional control of regulatory T-cell differentiation. Cold Spring Harb Symp Quant Biol. 2013;78:215–22.PubMedCrossRef
66.
Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27(4):635–46.PubMedCrossRef
67.
68.
69.
Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol. 2003;4(12):1206–12.PubMedCrossRef
70.
Wang H, Franco F, Ho PC. Metabolic regulation of Tregs in Cancer: opportunities for immunotherapy. Trends Cancer. 2017;3(8):583–92.PubMedCrossRef
71.
Jang JE, Hajdu CH, Liot C, Miller G, Dustin ML, Bar-Sagi D. Crosstalk between regulatory T cells and tumor-associated dendritic cells negates anti-tumor immunity in pancreatic Cancer. Cell Rep. 2017;20(3):558–71.PubMedCrossRef
72.
Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 1999;397(6716):263–6.PubMedCrossRef
73.
de Jong YP, Rietdijk ST, Faubion WA, Abadia-Molina AC, Clarke K, Mizoguchi E, Tian J, Delaney T, Manning S, Gutierrez-Ramos JC, et al. Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis. Int Immunol. 2004;16(2):205–13.
74.
Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257–65.PubMedPubMedCentralCrossRef
75.
Kishore M, Cheung KCP, Fu H, Bonacina F, Wang G, Coe D, Ward EJ, Colamatteo A, Jangani M, Baragetti A, et al. Regulatory T cell migration is dependent on Glucokinase-mediated glycolysis. Immunity. 2017;47(5):875–89.e10.
76.
Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, Warmoes MO, de Cubas AA, MacIver NJ, Locasale JW, et al. Foxp3 and toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol. 2016;17(12):1459–66.PubMedPubMedCentralCrossRef
77.
78.
Ouyang W, Liao W, Luo CT, Yin N, Huse M, Kim MV, Peng M, Chan P, Ma Q, Mo Y, et al. Novel Foxo1-dependent transcriptional programs control Treg cell function. Nature. 2012;491(7425):554–9.PubMedPubMedCentralCrossRef
79.
Kerdiles YM, Stone EL, Beisner DR, McGargill MA, Ch'en IL, Stockmann C, Katayama CD, Hedrick SM. Foxo transcription factors control regulatory T cell development and function. Immunity. 2010;33(6):890–904.PubMedPubMedCentralCrossRef
80.
Angelin A, Gil-de-Gómez L, Dahiya S, Jiao J, Guo L, Levine MH, Wang Z, Quinn WJ 3rd, Kopinski PK, Wang L, et al. Foxp3 reprograms T cell metabolism to function in low-glucose, High-Lactate Environments. Cell Metab. 2017;25(6):1282–93.e7.PubMedPubMedCentralCrossRef
81.
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. 2011;35(6):871–82.PubMedPubMedCentralCrossRef
82.
83.
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186(6):3299–03.PubMedCrossRef
84.
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. 2015;6:6692.
85.
Howie D, Cobbold SP, Adams E, Ten Bokum A, Necula AS, Zhang W, Huang H, Roberts DJ, Thomas B, Hester SS, et al. Foxp3 drives oxidative phosphorylation and protection from lipotoxicity. JCI Insight. 2017;2(3):e89160.
86.
Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, Wang CR, Schumacker PT, Licht JD, Perlman H, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38(2):225–36.PubMedPubMedCentralCrossRef
87.
88.
Jiang BH, Semenza GL, Bauer C, Marti HH. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol. 1996;271(4 Pt 1):C1172–80.CrossRef
89.
90.
Kaluz S, Kaluzova M, Stanbridge EJ. Regulation of gene expression by hypoxia: integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element. Clin Chim Acta. 2008;395(1–2):6–13.PubMedPubMedCentralCrossRef
91.
Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, Coscia C, Iessi E, Logozzi M, Molinari A, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem. 2009;284(49):34211–22.PubMedCrossRefPubMedCentral
92.
93.
King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer. 2012;12:421.
94.
Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, Gimotty PA, Gilks CB, Lal P, Zhang L,et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 2011;475(7355):226–30.PubMedCrossRef
95.
Ren L, Yu Y, Wang L, Zhu Z, Lu R, Yao Z. Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth in liver cancer. Oncotarget. 2016;7(46):75763–73.
96.
Yan M, Jene N, Byrne D, Millar EK, O'Toole SA, McNeil CM, Bates GJ, Harris AL, Banham AH, Sutherland RL, et al. Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res. 2011;13(2):R47.
97.
Wei S, Kryczek I, Edwards RP, Zou L, Szeliga W, Banerjee M, Cost M, Cheng P, Chang A, Redman B, et al. Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res. 2007;67(15):7487–94.PubMedCrossRef
98.
Wald O, Izhar U, Amir G, Avniel S, Bar-Shavit Y, Wald H, Weiss ID, Galun E, Peled A. CD4+CXCR4highCD69+ T cells accumulate in lung adenocarcinoma. J Immunol. 2006;177(10):6983–90.PubMedCrossRef
99.
Shimizu Y, Dobashi K, Imai H, Sunaga N, Ono A, Sano T, Hikino T, Shimizu K, Tanaka S, Ishizuka T, et al.CXCR4+FOXP3+CD25+ lymphocytes accumulate in CXCL12-expressing malignant pleural mesothelioma. Int J Immunopathol Pharmacol. 2009;22(1):43–51.CrossRef
100.
Mrizak D, Martin N, Barjon C, Jimenez-Pailhes AS, Mustapha R, Niki T, Guigay J, Pancré V, de Launoit Y, Busson P, et al. Effect of nasopharyngeal carcinoma-derived exosomes on human regulatory T cells. J Natl Cancer Inst. 2014;107(1):363.
101.
Ben-Shoshan J, Maysel-Auslender S, Mor A, Keren G, George J. Hypoxia controls CD4+CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. Eur J Immunol. 2008;38(9):2412–8.
102.
Wu J, Cui H, Zhu Z, Wang L, Li H, Wang D. Effect of HIF1alpha on Foxp3 expression in CD4+ CD25- T lymphocytes. Microbiol Immunol. 2014;58(7):409–15.PubMedCrossRef
103.
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. 2012;109(41):E2784–93.CrossRef
104.
Fong GH, Takeda K. Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008;15(4):635–41.PubMedCrossRef
105.
Deng B, Zhu JM, Wang Y, Liu TT, Ding YB, Xiao WM, Lu GT, Bo P, Shen XZ. Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-beta1 in gastric cancer. PLoS One. 2013;8(5):e63777.PubMedPubMedCentralCrossRef
106.
Chen J, Jiang CC, Jin L, Zhang XD. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol. 2016;27(3):409–16.PubMedCrossRef
107.
Ruf M, Moch H, Schraml P. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int J Cancer. 2016;139(2):396–403.PubMedCrossRef
108.
Yamada N, Kuranaga Y, Kumazaki M, Shinohara H, Taniguchi K, Akao Y. Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression. Oncotarget. 2016;7(19):27033–43.
109.
Huber V, Fais S, Iero M, Lugini L, Canese P, Squarcina P, Zaccheddu A, Colone M, Arancia G, Gentile M, et al. Human colorectal Cancer cells induce T-cell death through release of Proapoptotic microvesicles: role in immune escape. Gastroenterology. 2005;128(7):1796–804.PubMedCrossRef
110.
Szajnik M1, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One. 2010;5(7):e11469.PubMedPubMedCentralCrossRef
111.
Yin Y, Cai X, Chen X, Liang H, Zhang Y, Li J, Wang Z, Chen X, Zhang W, Yokoyama S, et al. Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth. Cell Res. 2014;24(10):1164–80.PubMedPubMedCentralCrossRef
112.
Brennan P1, Babbage JW, Burgering BM, Groner B, Reif K, Cantrell DA. Phosphatidylinositol 3-Kinase Couples the Interleukin-2 Receptor to the Cell Cycle Regulator E2F. Immunity. 1997;7(5):679–89.PubMedCrossRef
113.
Huynh A, DuPage M, Priyadharshini B, Sage PT, Quiros J, Borges CM, Townamchai N, Gerriets VA, Rathmell JC, Sharpe AH, et al. Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat Immunol. 2015;16(2):188–96.PubMedPubMedCentralCrossRef
114.
Bensinger SJ, Walsh PT, Zhang J, Carroll M, Parsons R, Rathmell JC, Thompson CB, Burchill MA, Farrar MA, Turka LA. Distinct IL-2 Receptor Signaling Pattern in CD4+CD25+ Regulatory T Cells. J Immunol. 2004;172(9): 5287–96.PubMedCrossRef
115.
Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004;21(4):527–38.PubMedCrossRef
116.
Liu ZM, Wang KP, Ma J, Guo Zheng S. The role of all-trans retinoic acid in the biology of Foxp3+ regulatory T cells. Cell Mol Immunol. 2015;12(5):553–7.CrossRef
117.
Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006;108(5):1571–9.PubMedPubMedCentralCrossRef
118.
Smith HA, Kang Y. The metastasis-promoting roles of tumor-associated immune cells. J Mol Med (Berl). 2013;91(4):411–29.CrossRef
119.
Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208(7):1367–76.PubMedPubMedCentralCrossRef
120.
Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146(5):772–84.PubMedPubMedCentralCrossRef
121.
122.
Peggs KS, Quezada SA, Korman AJ, Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol. 2006;18(2):206–13.PubMedCrossRef
123.
124.
Zhuo C, Xu Y, Ying M, Li Q, Huang L, Li D, Cai S, Li B. FOXP3+ Tregs: heterogeneous phenotypes and conflicting impacts on survival outcomes in patients with colorectal cancer. Immunol Res. 2015;61(3):338–47.PubMedCrossRef
125.
Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006;12(2):465–72.PubMedCrossRef
126.
Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.PubMedCrossRef
127.
Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, Maeda Y, Hamaguchi M, Ohkura N, Sato E, et al. Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med. 2016;22(6):679–84.PubMedCrossRef
128.
129.
130.
Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, Zhao L, Vatan L, Shao I, Szeliga W, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18(12):1332–41.PubMedPubMedCentralCrossRef
131.
shida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30(8):837–42.
132.
Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, Miranda Rota E, Dahan R, Georgiou A, Sledzinska A, et al. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity. 2017;46(4):577–86.
133.
Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115(12):3623–33.PubMedPubMedCentralCrossRef
134.
Nakagawa H, Sido JM, Reyes EE, Kiers V, Cantor H, Kim HJ. Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity. Proc Natl Acad Sci USA. 2016;113(22):6248–53.CrossRef
135.
Li B, Saouaf SJ, Samanta A, Shen Y, Hancock WW, Greene MI. Biochemistry and therapeutic implications of mechanisms involved in FOXP3 activity in immune suppression. Curr Opin Immunol. 2007;19(5):583–8.PubMedCrossRef
136.
Park CS, Bang BR, Kwon HS, Moon KA, Kim TB, Lee KY, Moon HB, Cho YS. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem Pharmacol. 2012;84(12):1660–70.PubMedCrossRef
Metadata
Title
Effects of tumor metabolic microenvironment on regulatory T cells
Authors
Yi-an Wang
Xiao-Ling Li
Yong-Zhen Mo
Chun-Mei Fan
Le Tang
Fang Xiong
Can Guo
Bo Xiang
Ming Zhou
Jian Ma
Xi Huang
Xu Wu
Yong Li
Gui-Yuan Li
Zhao-yang Zeng
Wei Xiong
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0913-y

Other articles of this Issue 1/2018

Molecular Cancer 1/2018 Go to the issue

Research

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

Research

Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

Research

Exosome–transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression

Review

FBXW7: a critical tumor suppressor of human cancers

Letter to the Editor

LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1

Letter to the Editor

Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits