Role of different immune cells and metabolic pathways in modulating the immune response in pancreatic cancer (Review)
- Authors:
- Nnenna Elebo
- Pascaline Fru
- Jones Omoshoro‑Jones
- Geoffrey Patrick Candy
- Ekene Emmanuel Nweke
-
Affiliations: Department of Surgery, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, Gauteng 2193, South Africa - Published online on: October 21, 2020 https://doi.org/10.3892/mmr.2020.11622
- Pages: 4981-4991
-
Copyright: © Elebo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Rawla P, Sunkara T and Gaduputi V: Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J Oncol. 10:10–27. 2019. View Article : Google Scholar : PubMed/NCBI | |
Ryan DP, Hong TS and Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med. 371:1039–1049. 2014. View Article : Google Scholar : PubMed/NCBI | |
Polireddy K and Chen Q: Cancer of the pancreas: Molecular pathways and current advancement in treatment. J Cancer. 7:1497–1514. 2016. View Article : Google Scholar : PubMed/NCBI | |
Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, et al: Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 467:1114–1147. 2010. View Article : Google Scholar : PubMed/NCBI | |
Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG and Karamouzis MV: Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 12:173–181. 2020. View Article : Google Scholar : PubMed/NCBI | |
Ghesquière B, Wong BW, Kuchnio A and Carmeliet P: Metabolism of stromal and immune cells in health and disease. Nature. 511:167–176. 2014. View Article : Google Scholar : PubMed/NCBI | |
Hato T and Dagher PC: How the innate immune system senses trouble and causes trouble. Clin J Am Soc Nephrol. 10:1459–1469. 2015. View Article : Google Scholar : PubMed/NCBI | |
Inman KS, Francis AA and Murray NR: Complex role for the immune system in initiation and progression of pancreatic cancer. World J Gastroenterol. 20:11160–11181. 2014. View Article : Google Scholar : PubMed/NCBI | |
Pearce EL and Pearce EJ: Metabolic pathways in immune cell activation and quiescence. Immunity. 38:633–643. 2013. View Article : Google Scholar : PubMed/NCBI | |
Odegaard JI and Chawla A: The immune system as a sensor of the metabolic state. Immunity. 38:644–654. 2013. View Article : Google Scholar : PubMed/NCBI | |
von Ahrens D, Bhagat TD, Nagrath D, Maitra A and Verma A: The role of stromal cancer-associated fibroblasts in pancreatic cancer. J Hematol Oncol. 10:762017. View Article : Google Scholar : PubMed/NCBI | |
Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, et al: CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas. 28:e26–e31. 2004. View Article : Google Scholar : PubMed/NCBI | |
Tjomsland V, Sandström P, Spångeus A, Messmer D, Emilsson J, Falkmer U, Falkmer S, Magnusson KE, Borch K and Larsson M: Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: An indicator of disease severity? BMC Cancer. 10:872010. View Article : Google Scholar : PubMed/NCBI | |
De Sanctis F, Solito S, Ugel S, Molon B, Bronte V and Marigo I: MDSCs in cancer: Conceiving new prognostic and therapeutic targets. Biochim Biophys Acta. 1865:35–48. 2016.PubMed/NCBI | |
Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ and Vonderheide RH: Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 21:822–835. 2012. View Article : Google Scholar : PubMed/NCBI | |
Padoan A, Plebani M and Basso D: Inflammation and pancreatic cancer: Focus on metabolism, cytokines, and immunity. Int J Mol Sci. 20:6762019. View Article : Google Scholar | |
Pergamo M and Miller G: Myeloid-derived suppressor cells and their role in pancreatic cancer. Cancer Gene Therapy. 24:100–105. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gabitass RF, Annels NE, Stocken DD, Pandha HA and Middleton GW: Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother. 60:1419–1430. 2011. View Article : Google Scholar : PubMed/NCBI | |
Dietl K, Renner K, Dettmer K, Timischl B, Eberhart K, Dorn C, Hellerbrand C, Kastenberger M, Kunz-Schughart LA, Oefner PJ, et al: Lactic acid and acidification inhibit TNF secretion and glycolysis of human monocytes. J Immunol. 184:1200–1209. 2010. View Article : Google Scholar : PubMed/NCBI | |
Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, Sakoda M, Ueno S, Natsugoe S and Takao S: Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 167:e211–e219. 2011. View Article : Google Scholar : PubMed/NCBI | |
Mielgo A and Schmid MC: Impact of tumour associated macrophages in pancreatic cancer. BMB Rep. 46:131–138. 2013. View Article : Google Scholar : PubMed/NCBI | |
Esposito I, Menicagli M, Funel N, Bergmann F, Boggi U, Mosca F, Bevilacqua G and Campani D: Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol. 57:630–636. 2004. View Article : Google Scholar : PubMed/NCBI | |
Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, Yoshimura A, Reindl W, Sipos B, Akira S, et al: Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 19:456–469. 2011. View Article : Google Scholar : PubMed/NCBI | |
Kim JS, Park YS, Kim JY, Kim YG, Kim YJ, Lee HK, Kim HS, Hong JT, Kim Y and Han SB: Inhibition of human pancreatic tumor growth by cytokine-induced killer cells in nude mouse xenograft model. Immune Netw. 12:247–252. 2012. View Article : Google Scholar : PubMed/NCBI | |
Liu L, Zhao G, Wu W, Rong Y, Jin D, Wang D, Lou W and Qin X: Low intratumoral regulatory T cells and high peritumoral CD8(+) T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy. Cancer Immunol Immunother. 65:73–82. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kurts C: Th17 cells: A third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant. 23:816–819. 2007. View Article : Google Scholar : PubMed/NCBI | |
Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, et al: Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 581:100–105. 2020. View Article : Google Scholar : PubMed/NCBI | |
Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, Corzo A, Cho HI, Celis E, Lennox B, et al: Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 16:880–886. 2010. View Article : Google Scholar : PubMed/NCBI | |
Ochi A, Nguyen AH, Bedrosian AS, Mushlin HM, Zarbakhsh S, Barilla R, Zambirinis CP, Fallon NC, Rehman A, Pylayeva-Gupta Y, et al: MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 209:1671–1687. 2012. View Article : Google Scholar : PubMed/NCBI | |
Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y and Hiraoka N: Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer. 108:914–923. 2013. View Article : Google Scholar : PubMed/NCBI | |
Hiraoka N, Onozato K, Kosuge T and Hirohashi S: Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 12:5423–5434. 2006. View Article : Google Scholar : PubMed/NCBI | |
Knutson KL and Disis ML: Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 54:721–728. 2005. View Article : Google Scholar : PubMed/NCBI | |
Wörmann SM, Diakopoulos KN, Lesina M and Algül H: The immune network in pancreatic cancer development and progression. Oncogene. 33:29562013. View Article : Google Scholar : PubMed/NCBI | |
Zou W and Restifo NP: TH17 cells in tumour immunity and immunotherapy. Nat Rev Immunol. 10:248–256. 2010. View Article : Google Scholar : PubMed/NCBI | |
Gnerlich JL, Mitchem JB, Weir JS, Sankpal NV, Kashiwagi H, Belt BA, Porembka MR, Herndon JM, Eberlein TJ, Goedegebuure P and Linehan DC: Induction of Th17 cells in the tumor microenvironment improves survival in a murine model of pancreatic cancer. J Immunol. 185:4063–4071. 2010. View Article : Google Scholar : PubMed/NCBI | |
He Q, Luo X, Huang Y and Sheikh MS: Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX-2 selective non-steroidal anti-inflammatory agent in Bax-deficient cells. Oncogene. 21:6032–6040. 2002. View Article : Google Scholar : PubMed/NCBI | |
He S, Fei M, Wu Y, Zheng D, Wan D, Wang L and Li D: Distribution and clinical significance of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients. Int J Mol Sci. 12:7424–7437. 2011. View Article : Google Scholar : PubMed/NCBI | |
De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Carlo VD, Doglioni C and Protti MP: Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med. 208:469–478. 2011. View Article : Google Scholar : PubMed/NCBI | |
Bellone G, Turletti A, Artusio E, Mareschi K, Carbone A, Tibaudi D, Robecchi A, Emanuelli G and Rodeck U: Tumor-associated transforming growth factor-β and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am J Pathol. 155:537–547. 1999. 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 and Rathmell JC: 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 | |
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. Eur J Immunol. 38:2438–2450. 2008. View Article : Google Scholar : PubMed/NCBI | |
Sakaguchi S, Miyara M, Costantino CM and Hafler DA: FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 10:490–500. 2010. View Article : Google Scholar : PubMed/NCBI | |
Walker LS and Sansom DM: The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 11:852–863. 2011. View Article : Google Scholar : PubMed/NCBI | |
Yamamoto T, Yanagimoto H, Satoi S, Toyokawa H, Hirooka S, Yamaki S, Yui R, Yamao J, Kim S and Kwon AH: Circulating CD4+CD25+ regulatory T cells in patients with pancreatic cancer. Pancreas. 41:409–415. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chang DZ, Ma Y, Ji B, Wang H, Deng D, Liu Y, Abbruzzese JL, Liu YJ, Logsdon CD and Hwu P: Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. Clin Cancer Res. 17:7015–7023. 2011. View Article : Google Scholar : PubMed/NCBI | |
Ito T, Amakawa R, Inaba M, Ikehara S, Inaba K and Fukuhara S: Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol. 166:2961–2969. 2001. View Article : Google Scholar : PubMed/NCBI | |
Duan X, Deng L, Chen X, Lu Y, Zhang Q, Zhang K, Hu Y, Zeng J and Sun W: Clinical significance of the immunostimulatory MHC class I chain-related molecule A and NKG2D receptor on NK cells in pancreatic cancer. Med Oncol. 28:466–474. 2011. View Article : Google Scholar : PubMed/NCBI | |
Cai SW, Yang SZ, Gao J, Pan K, Chen JY, Wang YL, Wei LX and Dong JH: Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma. Surgery. 149:576–584. 2011. View Article : Google Scholar : PubMed/NCBI | |
Strouch MJ, Cheon EC, Salabat MR, Krantz SB, Gounaris E, Melstrom LG, Dangi-Garimella S, Wang E, Munshi HG, Khazaie K and Bentrem DJ: Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 16:2257–2265. 2010. View Article : Google Scholar : PubMed/NCBI | |
Feig C, Gopinathan A, Neesse A, Chan DS, Cook N and Tuveson DA: The pancreas cancer microenvironment. Clin Cancer Res. 18:4266–4276. 2012. View Article : Google Scholar : PubMed/NCBI | |
Stopa BK, Kusiak AA, Szopa DM, Ferdek EP and Jakubowska AM: Pancreatic cancer and its microenvironment-recent advances and current controversies. Int J Mol Sci. 21:32182020. View Article : Google Scholar | |
Li KY, Yuan JL, Trafton D, Wang JX, Niu N, Yuan CH, Liu XB and Zheng L: Pancreatic ductal adenocarcinoma immune microenvironment and immunotherapy prospects. Chronic Dis Transl Med. 6:6–17. 2020.PubMed/NCBI | |
Li X, Wenes M, Romero P, Huang SC, Fendt SM and Ho PC: Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 16:425–441. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yao W, Maitra A and Ying H: Recent insights into the biology of pancreatic cancer. EBioMedicine. 53:1026552020. View Article : Google Scholar : PubMed/NCBI | |
O'Neill LAJ, Kishton RJ and Rathmell J: A guide to immunometabolism for immunologists. Nat Rev Immunol. 16:553–565. 2016. View Article : Google Scholar : PubMed/NCBI | |
Palmer CS, Ostrowski M, Balderson B, Christian N and Crowe SM: Glucose metabolism regulates T cell activation, differentiation, and functions. Front Immunol. 6:12015. View Article : Google Scholar : PubMed/NCBI | |
Chung JC, Oh MJ, Choi SH and Bae CD: Proteomic analysis to identify biomarker proteins in pancreatic ductal adenocarcinoma. ANZ J Surg. 78:245–251. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yoon DY, Buchler P, Saarikoski ST, Hines OJ, Reber HA and Hankinson O: Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem Biophys Res Commun. 288:882–886. 2001. View Article : Google Scholar : PubMed/NCBI | |
Natsuizaka M, Ozasa M, Darmanin S, Miyamoto M, Kondo S, Kamada S, Shindoh M, Higashino F, Suhara W, Koide H, et al: Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia. Exp Cell Res. 313:3337–3348. 2007. View Article : Google Scholar : PubMed/NCBI | |
Cameron ME, Yakovenko A and Trevino JG: Glucose and lactate transport in pancreatic cancer: Glycolytic metabolism revisited. J Oncol. 2018:62148382018. 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 | |
Warburg O, Wind F and Negelein E: The metabolism of tumors in the body. J Gen Physiol. 8:519–530. 1927. View Article : Google Scholar : PubMed/NCBI | |
Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, Cyrus N, Brokowski CE, Eisenbarth SC, Phillips GM, et al: Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 513:559–563. 2014. View Article : Google Scholar : PubMed/NCBI | |
Choi SYC, Collins CC, Gout PW and Wang Y: Cancer-generated lactic acid: A regulatory, immunosuppressive metabolite? J Pathol. 230:350–355. 2013. View Article : Google Scholar : PubMed/NCBI | |
Mills EL and O'Neill LA: Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur J Immunol. 46:13–21. 2016. View Article : Google Scholar : PubMed/NCBI | |
Rodríguez-Prados JC, Través PG, Cuenca J, Rico D, Aragonés J, Martín-Sanz P, Cascante M and Boscá L: Substrate fate in activated macrophages: A comparison between innate, classic, and alternative activation. J Immunol. 185:605–614. 2010. View Article : Google Scholar : PubMed/NCBI | |
Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, et al: Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity. 41:14–20. 2014. View Article : Google Scholar : PubMed/NCBI | |
Li Y and Zhu B: Editorial: Metabolism of cancer cells and immune cells in the tumor microenvironment. Front Immunol. 9:30802018. 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 | |
MacIver NJ, Michalek RD and Rathmell JC: Metabolic regulation of T lymphocytes. Annu Rev Immunol. 31:259–283. 2013. View Article : Google Scholar : PubMed/NCBI | |
Waickman AT and Powell JD: mTOR, metabolism, and the regulation of T-cell differentiation and function. Immunol Rev. 249:43–58. 2012. View Article : Google Scholar : PubMed/NCBI | |
Mao Z and Zhang W: Role of mTOR in glucose and lipid metabolism. Int J Mol Sci. 19:20432018. View Article : Google Scholar | |
Ersahin T, Tuncbag N and Cetin-Atalay R: The PI3K/AKT/mTOR interactive pathway. Mol Biosyst. 11:1946–1954. 2015. View Article : Google Scholar : PubMed/NCBI | |
Doughty CA, Bleiman BF, Wagner DJ, Dufort FJ, Mataraza JM, Roberts MF and Chiles TC: Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: Role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth. Blood. 107:4458–4465. 2006. View Article : Google Scholar : PubMed/NCBI | |
Rodríguez-Espinosa O, Rojas-Espinosa O, Moreno-Altamirano MMB, López-Villegas EO and Sánchez-García FJ: Metabolic requirements for neutrophil extracellular traps formation. Immunology. 145:213–224. 2015. View Article : Google Scholar : PubMed/NCBI | |
Dallal RM, Christakos P, Lee K, Egawa S, Son YI and Lotze MT: Paucity of dendritic cells in pancreatic cancer. Surgery. 131:135–138. 2002. View Article : Google Scholar : PubMed/NCBI | |
Banchereau J and Steinman RM: Dendritic cells and the control of immunity. Nature. 392:245–252. 1998. View Article : Google Scholar : PubMed/NCBI | |
Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, Cross JR, Jung E, Thompson CB, Jones RG and Pearce EJ: Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood. 115:4742–4749. 2010. View Article : Google Scholar : PubMed/NCBI | |
Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, Redmann V, Freitas TC, Blagih J, van der Windt GJ, et al: TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKε supports the anabolic demands of dendritic cell activation. Nat Immunol. 15:323–332. 2014. View Article : Google Scholar : PubMed/NCBI | |
Martínez-Reyes I and Chandel NS: Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 11:1022020. View Article : Google Scholar : PubMed/NCBI | |
Reyes-Castellanos G, Masoud R and Carrier A: Mitochondrial metabolism in PDAC: From better knowledge to new targeting strategies. Biomedicines. 8:2702020. View Article : Google Scholar | |
Laurenti G and Tennant DA: Isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH): Three players for one phenotype in cancer? Biochem Soc Trans. 44:1111–1116. 2016. View Article : Google Scholar : PubMed/NCBI | |
Waitkus MS, Diplas BH and Yan H: Biological role and therapeutic potential of IDH mutations in cancer. Cancer Cell. 34:186–195. 2018. View Article : Google Scholar : PubMed/NCBI | |
Nogueira V and Hay N: Molecular pathways: Reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin Cancer Res. 19:4309–4314. 2013. View Article : Google Scholar : PubMed/NCBI | |
Schlichtholz B, Turyn J, Goyke E, Biernacki M, Jaskiewicz K, Sledzinski Z and Swierczynski J: Enhanced citrate synthase activity in human pancreatic cancer. Pancreas. 30:99–104. 2005. View Article : Google Scholar : PubMed/NCBI | |
Swierczynski J, Hebanowska A and Sledzinski T: Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer. World J Gastroenterol. 20:2279–2303. 2014. View Article : Google Scholar : PubMed/NCBI | |
Halabe Bucay A: Hypothesis proved...citric acid (citrate) does improve cancer: A case of a patient suffering from medullary thyroid cancer. Med Hypotheses. 73:2712009. View Article : Google Scholar : PubMed/NCBI | |
Amedei A, Niccolai E and Prisco D: Pancreatic cancer: Role of the immune system in cancer progression and vaccine-based immunotherapy. Hum Vaccin Immunother. 10:3354–3368. 2014. View Article : Google Scholar : PubMed/NCBI | |
Patra KC and Hay N: The pentose phosphate pathway and cancer. Trends Biochem Sci. 39:347–354. 2014. View Article : Google Scholar : PubMed/NCBI | |
Liu H, Huang D, McArthur DL, Boros LG, Nissen N and Heaney AP: Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res. 70:6368–6376. 2010. View Article : Google Scholar : PubMed/NCBI | |
Shukla SK, Purohit V, Mehla K, Gunda V, Chaika NV, Vernucci E, King RJ, Abrego J, Goode GD, Dasgupta A, et al: MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell. 32:71–87.e7. 2017. View Article : Google Scholar : PubMed/NCBI | |
Haschemi A, Kosma P, Gille L, Evans CR, Burant CF, Starkl P, Knapp B, Haas R, Schmid JA, Jandl C, et al: The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15:813–826. 2012. View Article : Google Scholar : PubMed/NCBI | |
Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, van den Bosch MW, Quinn SR, Domingo-Fernandez R, Johnston DG, et al: Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 21:65–80. 2015. View Article : Google Scholar : PubMed/NCBI | |
Fernandez-Zapico M, Kim DW, Philip P, Vandell A, Eckard J, Korn R, Del Priore G and Simeone D: Abstract B15: Therapeutic potential of targeting amino acid metabolism in pancreatic cancer. Cancer Res. 79:B152019. | |
Altan B, Kaira K, Watanabe A, Kubo N, Bao P, Dolgormaa G, Bilguun EO, Araki K, Kanai Y, Yokobori T, et al: Relationship between LAT1 expression and resistance to chemotherapy in pancreatic ductal adenocarcinoma. Cancer Chemother Pharmacol. 81:141–153. 2018. View Article : Google Scholar : PubMed/NCBI | |
Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, Grabocka E, Nofal M, Drebin JA, Thompson CB, et al: Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature. 497:633–637. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ananieva EA and Wilkinson AC: Branched-chain amino acid metabolism in cancer. Curr Opin Clin Nutr Metab Care. 21:64–70. 2018. View Article : Google Scholar : PubMed/NCBI | |
Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al: Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 5:e102502016. View Article : Google Scholar : PubMed/NCBI | |
Kamphorst JJ, Nofal M, Commisso C, Hackett SR, Lu W, Grabocka E, Vander Heiden MG, Miller G, Drebin JA, Bar-Sagi D, et al: Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 75:544–553. 2015. View Article : Google Scholar : PubMed/NCBI | |
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. 496:101–105. 2013. View Article : Google Scholar : PubMed/NCBI | |
Singer K, Cheng WC, Kreutz M, Ho PC and Siska PJ: Immunometabolism in cancer at a glance. Dis Models Mech. 11:dmm0342722018. View Article : Google Scholar | |
Sinclair LV, Rolf J, Emslie E, Shi Y-B, Taylor PM and Cantrell DA: Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol. 14:500–508. 2013. View Article : Google Scholar : PubMed/NCBI | |
Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frédérick R, De Plaen E, Uyttenhove C, Wouters J, Masereel B and Van den Eynde BJ: Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci USA. 109:24972012. View Article : Google Scholar : PubMed/NCBI | |
Cluntun AA, Lukey MJ, Cerione RA and Locasale JW: Glutamine metabolism in cancer: Understanding the heterogeneity. Trends Cancer. 3:169–180. 2017. View Article : Google Scholar : PubMed/NCBI | |
Nzeako UC and Gores GJ: Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer. 94:1903–1904. 2002. View Article : Google Scholar : PubMed/NCBI | |
Asano T, Shoda J, Ueda T, Kawamoto T, Todoroki T, Shimonishi M, Tanabe T, Sugimoto Y, Ichikawa A, Mutoh M, et al: Expressions of cyclooxygenase-2 and prostaglandin E-receptors in carcinoma of the gallbladder: Crucial role of arachidonate metabolism in tumor growth and progression. Clin Cancer Res. 8:1157–1167. 2002.PubMed/NCBI | |
Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML and Sinicrope FA: Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines. Cancer Res. 59:4356–4362. 1999.PubMed/NCBI | |
DuBois RN, Awad J, Morrow J, Roberts LJ II and Bishop PR: Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester. J Clin Invest. 93:493–498. 1994. View Article : Google Scholar : PubMed/NCBI | |
Sato T, Nakajima H, Fujio K and Mori Y: Enhancement of prostaglandin E2 production by epidermal growth factor requires the coordinate activation of cytosolic phospholipase A2 and cyclooxygenase 2 in human squamous carcinoma A431 cells. Prostaglandins. 53:355–369. 1997. View Article : Google Scholar : PubMed/NCBI | |
O'Sullivan D, van der Windt GJW, Huang SC, Curtis JD, Chang CH, Buck MD, Qiu J, Smith AM, Lam WY, DiPlato LM, et al: Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity. 41:75–88. 2014. View Article : Google Scholar : PubMed/NCBI | |
Zhang A, Sun H, Wang P, Han Y and Wang X: Modern analytical techniques in metabolomics analysis. Analyst. 137:293–300. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA and Thompson CB: ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 8:311–321. 2005. View Article : Google Scholar : PubMed/NCBI | |
Tadros S, Shukla SK, King RJ, Gunda V, Vernucci E, Abrego J, Chaika NV, Yu F, Lazenby AJ, Berim L, et al: De novo lipid synthesis facilitates gemcitabine resistance through endoplasmic reticulum stress in pancreatic cancer. Cancer Res. 77:5503–5517. 2017. View Article : Google Scholar : PubMed/NCBI | |
Walter K, Hong SM, Nyhan S, Canto M, Fedarko N, Klein A, Griffith M, Omura N, Medghalchi S, Kuhajda F and Goggins M: Serum fatty acid synthase as a marker of pancreatic neoplasia. Cancer Epidemiol Biomarkers Prev. 18:2380–2385. 2009. View Article : Google Scholar : PubMed/NCBI | |
Coleman RA, Lewin TM, Van Horn CG and Gonzalez-Baró MR: Do long-chain acyl-CoA synthetases regulate fatty acid entry into synthetic versus degradative pathways? J Nutr. 132:2123–2126. 2002. View Article : Google Scholar : PubMed/NCBI | |
Macášek J, Vecka M, Žák A, Urbánek M, Krechler T, Petruželka L, Staňková B and Zeman M: Plasma fatty acid composition in patients with pancreatic cancer: Correlations to clinical parameters. Nutr Cancer. 64:946–955. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chung YT, Matkowskyj KA, Li H, Bai H, Zhang W, Tsao MS, Liao J and Yang GY: Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma. Mod Pathol. 25:758–766. 2012. View Article : Google Scholar : PubMed/NCBI | |
Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, Lac S, Borge L, Roques J, Gayet O, et al: Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 112:2473–2478. 2015. View Article : Google Scholar : PubMed/NCBI | |
Alistar AT, Morris B, Harrison L, Bickenbach K, Starker L, Ginder N, McIlwain L, Luther S, Pardee TS and Alpert J: A single-arm, open-label, phase I study of CPI-613 (Devimistat) in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic adenocarcinoma. J Clin Oncol. 38:4635. 2020. View Article : Google Scholar | |
Philip PA, Buyse ME, Alistar AT, Rocha Lima CMSP, Luther S, Pardee TS and Van Cutsem E: Avenger 500, a phase III open-label randomized trial of the combination of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. J Clin Oncol. 37:TPS4792019. View Article : Google Scholar | |
O'Donnell JS, Massi D, Teng MWL and Mandala M: PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol. 48:91–103. 2018. View Article : Google Scholar : PubMed/NCBI | |
Jin J and Zhao Q: Emerging role of mTOR in tumor immune contexture: Impact on chemokine-related immune cells migration. Theranostics. 10:6231–6244. 2020. View Article : Google Scholar : PubMed/NCBI | |
Allard B, Longhi MS, Robson SC and Stagg J: The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol Rev. 276:121–144. 2017. View Article : Google Scholar : PubMed/NCBI | |
Arina A and Bronte V: Myeloid-derived suppressor cell impact on endogenous and adoptively transferred T cells. Curr Opin Immunol. 33:120–125. 2015. View Article : Google Scholar : PubMed/NCBI | |
Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, et al: LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 24:657–671. 2016. View Article : Google Scholar : PubMed/NCBI | |
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. 204:1257–1265. 2007. View Article : Google Scholar : PubMed/NCBI | |
Hiraoka N, Toue S, Okamoto C, Kikuchi S, Ino Y, Yamazaki-Itoh R, Esaki M, Nara S, Kishi Y, Imaizumi A, et al: Tissue amino acid profiles are characteristic of tumor type, malignant phenotype, and tumor progression in pancreatic tumors. Sci Rep. 9:98162019. View Article : Google Scholar : PubMed/NCBI | |
Hossain F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss K, Valle LD, Trillo-Tinoco J, Maj T, Zou W, et al: Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res. 3:1236–1247. 2015. View Article : Google Scholar : PubMed/NCBI | |
Kalinski P: Regulation of immune responses by prostaglandin E2. J Immunol. 188:21–28. 2012. View Article : Google Scholar : PubMed/NCBI | |
Korangath P, Teo WW, Sadik H, Han L, Mori N, Huijts CM, Wildes F, Bharti S, Zhang Z, Santa-Maria CA, et al: Targeting glutamine metabolism in breast cancer with aminooxyacetate. Clin Cancer Res. 21:3263–3273. 2015. View Article : Google Scholar : PubMed/NCBI | |
Leone RD and Emens LA: Targeting adenosine for cancer immunotherapy. J Immunother Cancer. 6:572018. View Article : Google Scholar : PubMed/NCBI | |
Li M, Tan SY and Wang XF: Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE2 synthesis and COX-2 expression. Oncol Rep. 32:2845–2853. 2014. View Article : Google Scholar : PubMed/NCBI | |
Liu WR, Tian MX, Yang LX, Lin YL, Jin L, Ding ZB, Shen YH, Peng YF, Gao DM, Zhou J, et al: PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma. Oncotarget. 6:846–861. 2015. View Article : Google Scholar : PubMed/NCBI | |
Mohammad GH, Olde Damink SW, Malago M, Dhar DK and Pereira SP: Pyruvate kinase M2 and lactate dehydrogenase A are overexpressed in pancreatic cancer and correlate with poor outcome. PLoS One. 11:e01516352016. 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 | |
Yu CP, Fu SF, Chen X, Ye J, Ye Y, Kong LD and Zhu Z: The clinicopathological and prognostic significance of IDO1 expression in human solid tumors: evidence from a systematic review and meta-analysis. Cell Physiol Biochem. 49:134–143. 2018. View Article : Google Scholar : PubMed/NCBI | |
Biswas SK: Metabolic reprogramming of immune cells in cancer progression. Immunity. 43:435–449. 2015. View Article : Google Scholar : PubMed/NCBI |