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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

The Tumor Immune Microenvironment plays a Key Role in Driving the Progression of Cholangiocarcinoma

Author(s): Ye Zhang, Hai-jiao Yan* and Jun Wu*

Volume 24, Issue 7, 2024

Published on: 11 January, 2024

Page: [681 - 700] Pages: 20

DOI: 10.2174/0115680096267791231115101107

Price: $65

Abstract

Cholangiocarcinoma (CCA) is an epithelial cancer distinguished by bile duct cell differentiation and is also a fibroproliferative tumor. It is characterized by a dense mesenchyme and a complex tumor immune microenvironment (TME). The TME comprises both cellular and non-cellular components. The celluar component includes CCA cells, immune cells and mesenchymal cells represented by the cancer-associated fibroblasts (CAFs), while the non-cellular component is represented by mesenchymal elements such as the extracellular matrix (ECM). Recent studies have demonstrated the important role of the TME in the development, progression, and treatment resistance of CCA. These cell-associated prognostic markers as well as intercellular connections, may serve as potential therapeutic targets and could inspire new treatment approaches for CCA in the future. This paper aims to summarize the current understanding of CCA's immune microenvironment, focusing on immune cells, mesenchymal cells, ECM, intercellular interactions, and metabolism within the microenvironment.

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Graphical Abstract

[1]
Banales, J.M.; Marin, J.J.G.; Lamarca, A.; Rodrigues, P.M.; Khan, S.A.; Roberts, L.R.; Cardinale, V.; Carpino, G.; Andersen, J.B.; Braconi, C.; Calvisi, D.F.; Perugorria, M.J.; Fabris, L.; Boulter, L.; Macias, R.I.R.; Gaudio, E.; Alvaro, D.; Gradilone, S.A.; Strazzabosco, M.; Marzioni, M.; Coulouarn, C.; Fouassier, L.; Raggi, C.; Invernizzi, P.; Mertens, J.C.; Moncsek, A.; Rizvi, S.; Heimbach, J.; Koerkamp, B.G.; Bruix, J.; Forner, A.; Bridgewater, J.; Valle, J.W.; Gores, G.J. Cholangiocarcinoma 2020: The next horizon in mechanisms and management. Nat. Rev. Gastroenterol. Hepatol., 2020, 17(9), 557-588.
[http://dx.doi.org/10.1038/s41575-020-0310-z] [PMID: 32606456]
[2]
Rimassa, L.; Personeni, N.; Aghemo, A.; Lleo, A. The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. J. Autoimmun., 2019, 100, 17-26.
[http://dx.doi.org/10.1016/j.jaut.2019.03.007] [PMID: 30862450]
[3]
Nakamura, H.; Arai, Y.; Totoki, Y.; Shirota, T.; Elzawahry, A.; Kato, M.; Hama, N.; Hosoda, F.; Urushidate, T.; Ohashi, S.; Hiraoka, N.; Ojima, H.; Shimada, K.; Okusaka, T.; Kosuge, T.; Miyagawa, S.; Shibata, T. Genomic spectra of biliary tract cancer. Nat. Genet., 2015, 47(9), 1003-1010.
[http://dx.doi.org/10.1038/ng.3375] [PMID: 26258846]
[4]
Xia, T.; Li, K.; Niu, N.; Shao, Y.; Ding, D.; Thomas, D.L.; Jing, H.; Fujiwara, K.; Hu, H.; Osipov, A.; Yuan, C.; Wolfgang, C.L.; Thompson, E.D.; Anders, R.A.; He, J.; Mou, Y.; Murphy, A.G.; Zheng, L. Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses. J. Hematol. Oncol., 2022, 15(1), 37.
[http://dx.doi.org/10.1186/s13045-022-01253-z] [PMID: 35346322]
[5]
Montal, R.; Sia, D.; Montironi, C.; Leow, W.Q.; Esteban-Fabró, R.; Pinyol, R.; Torres-Martin, M.; Bassaganyas, L.; Moeini, A.; Peix, J.; Cabellos, L.; Maeda, M.; Villacorta-Martin, C.; Tabrizian, P.; Rodriguez-Carunchio, L.; Castellano, G.; Sempoux, C.; Minguez, B.; Pawlik, T.M.; Labgaa, I.; Roberts, L.R.; Sole, M.; Fiel, M.I.; Thung, S.; Fuster, J.; Roayaie, S.; Villanueva, A.; Schwartz, M.; Llovet, J.M. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J. Hepatol., 2020, 73(2), 315-327.
[http://dx.doi.org/10.1016/j.jhep.2020.03.008] [PMID: 32173382]
[6]
Farhood, B.; Najafi, M.; Mortezaee, K. CD8 + cytotoxic T lymphocytes in cancer immunotherapy: A review. J. Cell. Physiol., 2019, 234(6), 8509-8521.
[http://dx.doi.org/10.1002/jcp.27782] [PMID: 30520029]
[7]
Brindley, P.J.; Bachini, M. Cholangiocarcinoma., 2021, 7(1), 65.
[8]
Chen, Z.; Yu, M.; Yan, J.; Guo, L.; Zhang, B.; Liu, S.; Lei, J.; Zhang, W.; Zhou, B.; Gao, J.; Yang, Z.; Li, X.; Zhou, J.; Fan, J.; Ye, Q.; Li, H.; Xu, Y.; Xiao, Y. PNOC Expressed by B cells in cholangiocarcinoma was survival related and LAIR2 Could Be a T cell exhaustion biomarker in tumor microenvironment: Characterization of immune microenvironment combining single-cell and bulk sequencing technology. Front. Immunol., 2021, 12, 647209.
[http://dx.doi.org/10.3389/fimmu.2021.647209] [PMID: 33841428]
[9]
Zhang, M.; Yang, H.; Wan, L.; Wang, Z.; Wang, H.; Ge, C.; Liu, Y.; Hao, Y.; Zhang, D.; Shi, G.; Gong, Y.; Ni, Y.; Wang, C.; Zhang, Y.; Xi, J.; Wang, S.; Shi, L.; Zhang, L.; Yue, W.; Pei, X.; Liu, B.; Yan, X. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. J. Hepatol., 2020, 73(5), 1118-1130.
[http://dx.doi.org/10.1016/j.jhep.2020.05.039] [PMID: 32505533]
[10]
Liu, D.; Heij, L.R.; Czigany, Z.; Dahl, E.; Lang, S.A.; Ulmer, T.F.; Luedde, T.; Neumann, U.P.; Bednarsch, J. The role of tumor-infiltrating lymphocytes in cholangiocarcinoma. J. Exp. Clin. Cancer Res., 2022, 41(1), 127.
[http://dx.doi.org/10.1186/s13046-022-02340-2] [PMID: 35392957]
[11]
Rowshanravan, B.; Halliday, N.; Sansom, D.M. CTLA-4: A moving target in immunotherapy. Blood, 2018, 131(1), 58-67.
[http://dx.doi.org/10.1182/blood-2017-06-741033] [PMID: 29118008]
[12]
Cao, H.; Huang, T.; Dai, M.; Kong, X.; Liu, H.; Zheng, Z.; Sun, G.; Sun, G.; Rong, D.; Jin, Z.; Tang, W.; Xia, Y. Tumor microenvironment and its implications for antitumor immunity in cholangiocarcinoma: Future perspectives for novel therapies. Int. J. Biol. Sci., 2022, 18(14), 5369-5390.
[http://dx.doi.org/10.7150/ijbs.73949] [PMID: 36147461]
[13]
Lv, B.; Wang, Y.; Ma, D.; Cheng, W.; Liu, J.; Yong, T.; Chen, H.; Wang, C. Immunotherapy: Reshape the tumor immune microenvironment. Front. Immunol., 2022, 13, 844142.
[http://dx.doi.org/10.3389/fimmu.2022.844142] [PMID: 35874717]
[14]
Borggrewe, M.; Grit, C.; Den Dunnen, W.F.A.; Burm, S.M.; Bajramovic, J.J.; Noelle, R.J.; Eggen, B.J.L.; Laman, J.D. VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases. Glia, 2018, 66(12), 2645-2658.
[http://dx.doi.org/10.1002/glia.23517] [PMID: 30306644]
[15]
Vivier, E.; Ugolini, S.; Blaise, D.; Chabannon, C.; Brossay, L. Targeting natural killer cells and natural killer T cells in cancer. Nat. Rev. Immunol., 2012, 12(4), 239-252.
[http://dx.doi.org/10.1038/nri3174] [PMID: 22437937]
[16]
Hinshaw, D.C.; Shevde, L.A. The tumor microenvironment innately modulates cancer progression. Cancer Res., 2019, 79(18), 4557-4566.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-3962] [PMID: 31350295]
[17]
Yuan, H.; Lin, Z.; Liu, Y.; Jiang, Y.; Liu, K.; Tu, M.; Yao, N.; Qu, C.; Hong, J. Intrahepatic cholangiocarcinoma induced M2-polarized tumor-associated macrophages facilitate tumor growth and invasiveness. Cancer Cell Int., 2020, 20(1), 586.
[http://dx.doi.org/10.1186/s12935-020-01687-w] [PMID: 33372604]
[18]
Noy, R.; Pollard, J.W. Tumor-associated macrophages: From mechanisms to therapy. Immunity, 2014, 41(1), 49-61.
[http://dx.doi.org/10.1016/j.immuni.2014.06.010] [PMID: 25035953]
[19]
Dehingia, K.; Hosseini, K.; Salahshour, S.; Baleanu, D. A detailed study on a tumor model with delayed growth of pro-tumor macrophages. Int. J. Appl. Comput. Math., 2022, 8(5), 245.
[http://dx.doi.org/10.1007/s40819-022-01433-y]
[20]
Fabris, L.; Perugorria, M.J.; Mertens, J.; Björkström, N.K.; Cramer, T.; Lleo, A.; Solinas, A.; Sänger, H.; Lukacs-Kornek, V.; Moncsek, A.; Siebenhüner, A.; Strazzabosco, M. The tumour microenvironment and immune milieu of cholangiocarcinoma. Liver Int., 2019, 39(S1), 63-78.
[http://dx.doi.org/10.1111/liv.14098] [PMID: 30907492]
[21]
Sun, J.; Lu, Q.; Sanmamed, M.F.; Wang, J. Siglec-15 as an emerging target for next-generation cancer immunotherapy. Clin. Cancer Res., 2021, 27(3), 680-688.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2925] [PMID: 32958700]
[22]
Henze, A.T.; Mazzone, M. The impact of hypoxia on tumor-associated macrophages. J. Clin. Invest., 2016, 126(10), 3672-3679.
[http://dx.doi.org/10.1172/JCI84427] [PMID: 27482883]
[23]
Wang, J.; Loeuillard, E.; Gores, G.J.; Ilyas, S.I. Cholangiocarcinoma: What are the most valuable therapeutic targets – cancer-associated fibroblasts, immune cells, or beyond T cells? Expert Opin. Ther. Targets, 2021, 25(10), 835-845.
[http://dx.doi.org/10.1080/14728222.2021.2010046] [PMID: 34806500]
[24]
Fabris, L.; Cadamuro, M.; Fouassier, L. Illuminate TWEAK/Fn14 pathway in intrahepatic cholangiocarcinoma: Another brick in the wall of tumor niche. J. Hepatol., 2021, 74(4), 771-774.
[http://dx.doi.org/10.1016/j.jhep.2020.12.019] [PMID: 33583626]
[25]
Yuan, D; Huang, S; Berger, E; Liu, L; Gross, N; Heinzmann, F Kupffer cell-derived Tnf triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer cell, 2017, 31(6), 771-789.
[http://dx.doi.org/10.1016/j.ccell.2017.05.006]
[26]
Yamada, D.; Rizvi, S.; Razumilava, N.; Bronk, S.F.; Davila, J.I.; Champion, M.D.; Borad, M.J.; Bezerra, J.A.; Chen, X.; Gores, G.J. IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6-sensitive mechanism. Hepatology, 2015, 61(5), 1627-1642.
[http://dx.doi.org/10.1002/hep.27687] [PMID: 25580681]
[27]
Huang, C.K.; Aihara, A.; Iwagami, Y.; Yu, T.; Carlson, R.; Koga, H.; Kim, M.; Zou, J.; Casulli, S.; Wands, J.R. Expression of transforming growth factor β1 promotes cholangiocarcinoma development and progression. Cancer Lett., 2016, 380(1), 153-162.
[http://dx.doi.org/10.1016/j.canlet.2016.05.038] [PMID: 27364974]
[28]
Goyal, L.; Zheng, H.; Yurgelun, M.B.; Abrams, T.A.; Allen, J.N.; Cleary, J.M.; Knowles, M.; Regan, E.; Reardon, A.; Khachatryan, A.; Jain, R.K.; Nardi, V.; Borger, D.R.; Duda, D.G.; Zhu, A.X. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma. Cancer, 2017, 123(11), 1979-1988.
[http://dx.doi.org/10.1002/cncr.30571] [PMID: 28192597]
[29]
Høgdall, D.; Lewinska, M.; Andersen, J.B. Desmoplastic tumor microenvironment and immunotherapy in cholangiocarcinoma. Trends Cancer, 2018, 4(3), 239-255.
[http://dx.doi.org/10.1016/j.trecan.2018.01.007] [PMID: 29506673]
[30]
Boulter, L.; Guest, R.V.; Kendall, T.J.; Wilson, D.H.; Wojtacha, D.; Robson, A.J.; Ridgway, R.A.; Samuel, K.; Van Rooijen, N.; Barry, S.T.; Wigmore, S.J.; Sansom, O.J.; Forbes, S.J. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J. Clin. Invest., 2015, 125(3), 1269-1285.
[http://dx.doi.org/10.1172/JCI76452] [PMID: 25689248]
[31]
Akhuba, L.; Tigai, Z.; Shek, D. Major hurdles of immune-checkpoint inhibitors in pancreatic ductal adenocarcinoma. Cancer Drug Resist., 2023, 6(2), 327-331.
[http://dx.doi.org/10.20517/cdr.2022.142] [PMID: 37457121]
[32]
Doedens, A.L.; Stockmann, C.; Rubinstein, M.P.; Liao, D.; Zhang, N.; DeNardo, D.G.; Coussens, L.M.; Karin, M.; Goldrath, A.W.; Johnson, R.S. Macrophage expression of hypoxia-inducible factor-1 α suppresses T-cell function and promotes tumor progression. Cancer Res., 2010, 70(19), 7465-7475.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1439] [PMID: 20841473]
[33]
Peinado, H.; Zhang, H.; Matei, I.R.; Costa-Silva, B.; Hoshino, A.; Rodrigues, G.; Psaila, B.; Kaplan, R.N.; Bromberg, J.F.; Kang, Y.; Bissell, M.J.; Cox, T.R.; Giaccia, A.J.; Erler, J.T.; Hiratsuka, S.; Ghajar, C.M.; Lyden, D. Pre-metastatic niches: Organ-specific homes for metastases. Nat. Rev. Cancer, 2017, 17(5), 302-317.
[http://dx.doi.org/10.1038/nrc.2017.6] [PMID: 28303905]
[34]
Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol., 2009, 9(3), 162-174.
[http://dx.doi.org/10.1038/nri2506] [PMID: 19197294]
[35]
Bronte, V.; Brandau, S.; Chen, S.H.; Colombo, M.P.; Frey, A.B.; Greten, T.F.; Mandruzzato, S.; Murray, P.J.; Ochoa, A.; Ostrand-Rosenberg, S.; Rodriguez, P.C.; Sica, A.; Umansky, V.; Vonderheide, R.H.; Gabrilovich, D.I. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun., 2016, 7(1), 12150.
[http://dx.doi.org/10.1038/ncomms12150] [PMID: 27381735]
[36]
Louis, C.; Edeline, J.; Coulouarn, C. Targeting the tumor microenvironment in cholangiocarcinoma: Implications for therapy. Expert Opin. Ther. Targets, 2021, 25(2), 153-162.
[http://dx.doi.org/10.1080/14728222.2021.1882998] [PMID: 33502260]
[37]
Sakuishi, K.; Jayaraman, P.; Behar, S.M.; Anderson, A.C.; Kuchroo, V.K. Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol., 2011, 32(8), 345-349.
[http://dx.doi.org/10.1016/j.it.2011.05.003] [PMID: 21697013]
[38]
Loeuillard, E.; Yang, J.; Buckarma, E.; Wang, J.; Liu, Y.; Conboy, C.; Pavelko, K.D.; Li, Y.; O’Brien, D.; Wang, C.; Graham, R.P.; Smoot, R.L.; Dong, H.; Ilyas, S. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. J. Clin. Invest., 2020, 130(10), 5380-5396.
[http://dx.doi.org/10.1172/JCI137110] [PMID: 32663198]
[39]
Tavazoie, MF; Pollack, I; Tanqueco, R; Ostendorf, BN; Reis, BS; Gonsalves, FC LXR/ApoE activation restricts innate immune suppression in cancer. Cell, 2018, 172(4), 825-840.
[40]
Fabris, L; Sato, K; Alpini, G; Strazzabosco, M. The tumor microenvironment in cholangiocarcinoma progression. Hepatology, 2021, 73, 75-85.
[http://dx.doi.org/10.1002/hep.31410]
[41]
Hu, Z.Q.; Zhou, Z.J.; Luo, C.B.; Xin, H.Y.; Li, J.; Yu, S.Y.; Zhou, S.L. Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection. Cancer Cell Int., 2020, 20(1), 582.
[http://dx.doi.org/10.1186/s12935-020-01676-z] [PMID: 33292317]
[42]
Diggs, L.P.; Ruf, B.; Ma, C.; Heinrich, B.; Cui, L.; Zhang, Q.; McVey, J.C.; Wabitsch, S.; Heinrich, S.; Rosato, U.; Lai, W.; Subramanyam, V.; Longerich, T.; Loosen, S.H.; Luedde, T.; Neumann, U.P.; Desar, S.; Kleiner, D.; Gores, G.; Wang, X.W.; Greten, T.F. CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma. J. Hepatol., 2021, 74(5), 1145-1154.
[http://dx.doi.org/10.1016/j.jhep.2020.11.037] [PMID: 33276030]
[43]
Lin, D.S.; Tian, L.; Tomei, S.; Amann-Zalcenstein, D.; Baldwin, T.M.; Weber, T.S.; Schreuder, J.; Stonehouse, O.J.; Rautela, J.; Huntington, N.D.; Taoudi, S.; Ritchie, M.E.; Hodgkin, P.D.; Ng, A.P.; Nutt, S.L.; Naik, S.H. Single-cell analyses reveal the clonal and molecular aetiology of Flt3L-induced emergency dendritic cell development. Nat. Cell Biol., 2021, 23(3), 219-231.
[http://dx.doi.org/10.1038/s41556-021-00636-7] [PMID: 33649477]
[44]
Björkström, N.K.; Ljunggren, H.G.; Michaëlsson, J. Emerging insights into natural killer cells in human peripheral tissues. Nat. Rev. Immunol., 2016, 16(5), 310-320.
[http://dx.doi.org/10.1038/nri.2016.34] [PMID: 27121652]
[45]
Jung, IH In vivo study of natural killer (NK) cell cytotoxicity against cholangiocarcinoma in a nude mouse model. in vivo, 2018, 32(4), 771-81.
[46]
Cazzetta, V.; Franzese, S.; Carenza, C.; Della Bella, S.; Mikulak, J.; Mavilio, D. Natural killer–dendritic cell interactions in liver cancer: Implications for immunotherapy. cancers, 2021, 13(9), 2184.
[http://dx.doi.org/10.3390/cancers13092184] [PMID: 34062821]
[47]
Fukuda, Y.; Asaoka, T.; Eguchi, H.; Yokota, Y.; Kubo, M.; Kinoshita, M.; Urakawa, S.; Iwagami, Y.; Tomimaru, Y.; Akita, H.; Noda, T.; Gotoh, K.; Kobayashi, S.; Hirata, M.; Wada, H.; Mori, M.; Doki, Y. Endogenous CXCL9 affects prognosis by regulating tumor-infiltrating natural killer cells in intrahepatic cholangiocarcinoma. Cancer Sci., 2020, 111(2), 323-333.
[http://dx.doi.org/10.1111/cas.14267] [PMID: 31799781]
[48]
Mantovani, S.; Oliviero, B.; Lombardi, A.; Varchetta, S.; Mele, D.; Sangiovanni, A.; Rossi, G.; Donadon, M.; Torzilli, G.; Soldani, C.; Porta, C.; Pedrazzoli, P.; Chiellino, S.; Santambrogio, R.; Opocher, E.; Maestri, M.; Bernuzzi, S.; Rossello, A.; Clément, S.; De Vito, C.; Rubbia-Brandt, L.; Negro, F.; Mondelli, M.U. Deficient natural killer cell NKp30-mediated function and altered NCR3 splice variants in hepatocellular carcinoma. Hepatology, 2019, 69(3), 1165-1179.
[http://dx.doi.org/10.1002/hep.30235] [PMID: 30153337]
[49]
Alnaggar, M.; Lin, M.; Mesmar, A.; Liang, S.; Qaid, A.; Xu, K.; Chen, J.; Niu, L.; Yin, Z. Allogenic natural killer cell immunotherapy combined with irreversible electroporation for stage IV hepatocellular carcinoma: Survival outcome. Cell. Physiol. Biochem., 2018, 48(5), 1882-1893.
[http://dx.doi.org/10.1159/000492509] [PMID: 30092590]
[50]
Chida, K.; Kawazoe, A.; Suzuki, T.; Kawazu, M.; Ueno, T.; Takenouchi, K.; Nakamura, Y.; Kuboki, Y.; Kotani, D.; Kojima, T.; Bando, H.; Mishima, S.; Kuwata, T.; Sakamoto, N.; Watanabe, J.; Mano, H.; Ikeda, M.; Shitara, K.; Endo, I.; Nakatsura, T.; Yoshino, T. Transcriptomic profiling of MSI-H/dMMR gastrointestinal tumors to identify determinants of responsiveness to Anti–PD-1 therapy. Clin. Cancer Res., 2022, 28(10), 2110-2117.
[http://dx.doi.org/10.1158/1078-0432.CCR-22-0041] [PMID: 35254400]
[51]
Akhuba, L.; Tigai, Z.; Shek, D. Where do we stand with immunotherapy for advanced pancreatic ductal adenocarcinoma: A synopsis of clinical outcomes. Biomedicines, 2022, 10(12), 3196.
[http://dx.doi.org/10.3390/biomedicines10123196] [PMID: 36551952]
[52]
Kennedy, L.; Hargrove, L.; Demieville, J.; Karstens, W.; Jones, H.; DeMorrow, S.; Meng, F.; Invernizzi, P.; Bernuzzi, F.; Alpini, G.; Smith, S.; Akers, A.; Meadows, V.; Francis, H. Blocking H1/H2 histamine receptors inhibits damage/fibrosis in Mdr2–/– mice and human cholangiocarcinoma tumorigenesis. Hepatology, 2018, 68(3), 1042-1056.
[http://dx.doi.org/10.1002/hep.29898] [PMID: 29601088]
[53]
Francis, H.; Onori, P.; Gaudio, E.; Franchitto, A.; DeMorrow, S.; Venter, J.; Kopriva, S.; Carpino, G.; Mancinelli, R.; White, M.; Meng, F.; Vetuschi, A.; Sferra, R.; Alpini, G. H3 histamine receptor–mediated activation of protein kinase cα inhibits the growth of cholangiocarcinoma in vitro and in vivo. Mol. Cancer Res., 2009, 7(10), 1704-1713.
[http://dx.doi.org/10.1158/1541-7786.MCR-09-0261] [PMID: 19825989]
[54]
Meng, F.; Han, Y.; Staloch, D.; Francis, T.; Stokes, A.; Francis, H. The H4 histamine receptor agonist, clobenpropit, suppresses human cholangiocarcinoma progression by disruption of epithelial mesenchymal transition and tumor metastasis. Hepatology, 2011, 54(5), 1718-1728.
[http://dx.doi.org/10.1002/hep.24573] [PMID: 21793031]
[55]
Petley, E.V.; Koay, H.F.; Henderson, M.A.; Sek, K.; Todd, K.L.; Keam, S.P.; Lai, J.; House, I.G.; Li, J.; Zethoven, M.; Chen, A.X.Y.; Oliver, A.J.; Michie, J.; Freeman, A.J.; Giuffrida, L.; Chan, J.D.; Pizzolla, A.; Mak, J.Y.W.; McCulloch, T.R.; Souza-Fonseca-Guimaraes, F.; Kearney, C.J.; Millen, R.; Ramsay, R.G.; Huntington, N.D.; McCluskey, J.; Oliaro, J.; Fairlie, D.P.; Neeson, P.J.; Godfrey, D.I.; Beavis, P.A.; Darcy, P.K. MAIT cells regulate NK cell-mediated tumor immunity. Nat. Commun., 2021, 12(1), 4746.
[http://dx.doi.org/10.1038/s41467-021-25009-4] [PMID: 34362900]
[56]
Fiori, M.E.; Di Franco, S.; Villanova, L.; Bianca, P.; Stassi, G.; De Maria, R. Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Mol. Cancer, 2019, 18(1), 70.
[http://dx.doi.org/10.1186/s12943-019-0994-2] [PMID: 30927908]
[57]
Prakash, J. Cancer-associated fibroblasts: Perspectives in cancer therapy. Trends Cancer, 2016, 2(6), 277-279.
[http://dx.doi.org/10.1016/j.trecan.2016.04.005] [PMID: 28741524]
[58]
Scholten, D.; Österreicher, C.H.; Scholten, A.; Iwaisako, K.; Gu, G.; Brenner, D.A.; Kisseleva, T. Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology, 2010, 139(3), 987-998.
[http://dx.doi.org/10.1053/j.gastro.2010.05.005] [PMID: 20546735]
[59]
Affo, S.; Nair, A.; Brundu, F.; Ravichandra, A.; Bhattacharjee, S.; Matsuda, M.; Chin, L.; Filliol, A.; Wen, W.; Song, X.; Decker, A.; Worley, J.; Caviglia, J.M.; Yu, L.; Yin, D.; Saito, Y.; Savage, T.; Wells, R.G.; Mack, M.; Zender, L.; Arpaia, N.; Remotti, H.E.; Rabadan, R.; Sims, P.; Leblond, A.L.; Weber, A.; Riener, M.O.; Stockwell, B.R.; Gaublomme, J.; Llovet, J.M.; Kalluri, R.; Michalopoulos, G.K.; Seki, E.; Sia, D.; Chen, X.; Califano, A.; Schwabe, R.F. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell, 2021, 39(6), 883.
[http://dx.doi.org/10.1016/j.ccell.2021.05.010] [PMID: 34129825]
[60]
Affo, S.; Yu, L.X.; Schwabe, R.F. The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer. Annu. Rev. Pathol., 2017, 12(1), 153-186.
[http://dx.doi.org/10.1146/annurev-pathol-052016-100322] [PMID: 27959632]
[61]
Sirica, A.E.; Strazzabosco, M.; Cadamuro, M. Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression. Adv. Cancer Res., 2021, 149, 321-387.
[http://dx.doi.org/10.1016/bs.acr.2020.10.005] [PMID: 33579427]
[62]
Bergeat, D.; Fautrel, A.; Turlin, B.; Merdrignac, A.; Rayar, M.; Boudjema, K.; Coulouarn, C.; Sulpice, L. Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma. J. Surg. Res., 2016, 203(2), 441-450.
[http://dx.doi.org/10.1016/j.jss.2016.03.044] [PMID: 27363654]
[63]
Yang, X.; Lin, Y.; Shi, Y.; Li, B.; Liu, W.; Yin, W.; Dang, Y.; Chu, Y.; Fan, J.; He, R. FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3–CCL2 signaling. Cancer Res., 2016, 76(14), 4124-4135.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2973] [PMID: 27216177]
[64]
Yangngam, S.; Thongchot, S.; Pongpaibul, A.; Vaeteewoottacharn, K.; Pinlaor, S.; Thuwajit, P.; Okada, S.; Thuwajit, C.; Thuwajit, C. High level of interleukin-33 in cancer cells and cancer-associated fibroblasts correlates with good prognosis and suppressed migration in cholangiocarcinoma. J. Cancer, 2020, 11(22), 6571-6581.
[http://dx.doi.org/10.7150/jca.48327] [PMID: 33046978]
[65]
Utaijaratrasmi, P.; Vaeteewoottacharn, K.; Tsunematsu, T.; Jamjantra, P.; Wongkham, S.; Pairojkul, C.; Khuntikeo, N.; Ishimaru, N.; Sirivatanauksorn, Y.; Pongpaibul, A.; Thuwajit, P.; Thuwajit, C.; Kudo, Y. The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells. Mol. Cancer, 2018, 17(1), 10.
[http://dx.doi.org/10.1186/s12943-018-0760-x] [PMID: 29347950]
[66]
Gentilini, A.; Pastore, M.; Marra, F.; Raggi, C. The role of stroma in cholangiocarcinoma: The intriguing interplay between fibroblastic component, immune cell subsets and tumor epithelium. Int. J. Mol. Sci., 2018, 19(10), 2885.
[http://dx.doi.org/10.3390/ijms19102885] [PMID: 30249019]
[67]
Cadamuro, M.; Brivio, S.; Mertens, J.; Vismara, M.; Moncsek, A.; Milani, C.; Fingas, C.; Cristina Malerba, M.; Nardo, G.; Dall’Olmo, L.; Milani, E.; Mariotti, V.; Stecca, T.; Massani, M.; Spirli, C.; Fiorotto, R.; Indraccolo, S.; Strazzabosco, M.; Fabris, L. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. J. Hepatol., 2019, 70(4), 700-709.
[http://dx.doi.org/10.1016/j.jhep.2018.12.004] [PMID: 30553841]
[68]
Aoki, S.; Inoue, K.; Klein, S.; Halvorsen, S.; Chen, J.; Matsui, A.; Nikmaneshi, M.R.; Kitahara, S.; Hato, T.; Chen, X.; Kawakubo, K.; Nia, H.T.; Chen, I.; Schanne, D.H.; Mamessier, E.; Shigeta, K.; Kikuchi, H.; Ramjiawan, R.R.; Schmidt, T.C.E.; Iwasaki, M.; Yau, T.; Hong, T.S.; Quaas, A.; Plum, P.S.; Dima, S.; Popescu, I.; Bardeesy, N.; Munn, L.L.; Borad, M.J.; Sassi, S.; Jain, R.K.; Zhu, A.X.; Duda, D.G. Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma. Gut, 2022, 71(1), 185-193.
[http://dx.doi.org/10.1136/gutjnl-2020-322493] [PMID: 33431577]
[69]
Ehling, J.; Tacke, F. Role of chemokine pathways in hepatobiliary cancer. Cancer Lett., 2016, 379(2), 173-183.
[http://dx.doi.org/10.1016/j.canlet.2015.06.017] [PMID: 26123664]
[70]
Vaquero, J.; Lobe, C.; Tahraoui, S.; Clapéron, A.; Mergey, M.; Merabtene, F.; Wendum, D.; Coulouarn, C.; Housset, C.; Desbois-Mouthon, C.; Praz, F.; Fouassier, L. The IGF2/IR/IGF1R Pathway in tumor cells and myofibroblasts mediates resistance to EGFR inhibition in cholangiocarcinoma. Clin. Cancer Res., 2018, 24(17), 4282-4296.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3725] [PMID: 29716918]
[71]
Flavell, R.A.; Sanjabi, S.; Wrzesinski, S.H.; Licona-Limón, P. The polarization of immune cells in the tumour environment by TGFβ. Nat. Rev. Immunol., 2010, 10(8), 554-567.
[http://dx.doi.org/10.1038/nri2808] [PMID: 20616810]
[72]
Zhong, W.; Tong, Y.; Li, Y.; Yuan, J.; Hu, S.; Hu, T.; Song, G. Mesenchymal stem cells in inflammatory microenvironment potently promote metastatic growth of cholangiocarcinoma via activating Akt/NF-κB signaling by paracrine CCL5. Oncotarget, 2017, 8(43), 73693-73704.
[http://dx.doi.org/10.18632/oncotarget.17793] [PMID: 29088737]
[73]
Ziani, L.; Safta-Saadoun, T.B.; Gourbeix, J.; Cavalcanti, A.; Robert, C.; Favre, G.; Chouaib, S.; Thiery, J. Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion. Oncotarget, 2017, 8(12), 19780-19794.
[http://dx.doi.org/10.18632/oncotarget.15540] [PMID: 28423623]
[74]
Razumilava, N.; Gradilone, S.A.; Smoot, R.L.; Mertens, J.C.; Bronk, S.F.; Sirica, A.E.; Gores, G.J. Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J. Hepatol., 2014, 60(3), 599-605.
[http://dx.doi.org/10.1016/j.jhep.2013.11.005] [PMID: 24239776]
[75]
Fingas, C.D.; Bronk, S.F.; Werneburg, N.W.; Mott, J.L.; Guicciardi, M.E.; Cazanave, S.C.; Mertens, J.C.; Sirica, A.E.; Gores, G.J. Myofibroblast-derived PDGF-BB promotes hedgehog survival signaling in cholangiocarcinoma cells. Hepatology, 2011, 54(6), 2076-2088.
[http://dx.doi.org/10.1002/hep.24588] [PMID: 22038837]
[76]
De Sanctis, F.; Ugel, S.; Facciponte, J.; Facciabene, A. The dark side of tumor-associated endothelial cells. Semin. Immunol., 2018, 35, 35-47.
[http://dx.doi.org/10.1016/j.smim.2018.02.002] [PMID: 29490888]
[77]
Yokota, K.; Serada, S.; Tsujii, S.; Toya, K.; Takahashi, T.; Matsunaga, T.; Fujimoto, M.; Uemura, S.; Namikawa, T.; Murakami, I.; Kobayashi, S.; Eguchi, H.; Doki, Y.; Hanazaki, K.; Naka, T. Anti-glypican-1 antibody–drug conjugate as potential therapy against tumor cells and tumor vasculature for glypican-1–positive cholangiocarcinoma. Mol. Cancer Ther., 2021, 20(9), 1713-1722.
[http://dx.doi.org/10.1158/1535-7163.MCT-21-0015] [PMID: 34224365]
[78]
Nair, A.; Ingram, N.; Verghese, E.T.; Wijetunga, I.; Markham, A.F.; Wyatt, J.; Prasad, K.R.; Coletta, P.L. CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma. Cell Oncol., 2020, 43(5), 835-845.
[http://dx.doi.org/10.1007/s13402-020-00530-8] [PMID: 32468445]
[79]
Xu, Y.; Leng, K.; Yao, Y.; Kang, P.; Liao, G.; Han, Y.; Shi, G.; Ji, D.; Huang, P.; Zheng, W.; Li, Z.; Li, J.; Huang, L.; Yu, L.; Zhou, Y.; Jiang, X.; Wang, H.; Li, C.; Su, Z.; Tai, S.; Zhong, X.; Wang, Z.; Cui, Y. A circular RNA, cholangiocarcinoma-associated circular RNA 1, contributes to cholangiocarcinoma progression, induces angiogenesis, and disrupts vascular endothelial barriers. Hepatology, 2021, 73(4), 1419-1435.
[http://dx.doi.org/10.1002/hep.31493] [PMID: 32750152]
[80]
Gentilini, A.; Lori, G.; Caligiuri, A.; Raggi, C.; Di Maira, G.; Pastore, M.; Piombanti, B.; Lottini, T.; Arcangeli, A.; Madiai, S.; Navari, N.; Banales, J.M.; Di Matteo, S.; Alvaro, D.; Duwe, L.; Andersen, J.B.; Tubita, A.; Tusa, I.; Di Tommaso, L.; Campani, C.; Rovida, E.; Marra, F. Extracellular signal-regulated kinase 5 regulates the malignant phenotype of cholangiocarcinoma cells. Hepatology, 2021, 74(4), 2007-2020.
[http://dx.doi.org/10.1002/hep.31888] [PMID: 33959996]
[81]
Alitalo, K. The lymphatic vasculature in disease. Nat. Med., 2011, 17(11), 1371-1380.
[http://dx.doi.org/10.1038/nm.2545] [PMID: 22064427]
[82]
Stacker, S.A.; Williams, S.P.; Karnezis, T.; Shayan, R.; Fox, S.B.; Achen, M.G. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat. Rev. Cancer, 2014, 14(3), 159-172.
[http://dx.doi.org/10.1038/nrc3677] [PMID: 24561443]
[83]
Haga, H.; Yan, I.K.; Takahashi, K.; Wood, J.; Zubair, A.; Patel, T. Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth. J. Extracell. Vesicles, 2015, 4(1), 24900.
[http://dx.doi.org/10.3402/jev.v4.24900] [PMID: 25557794]
[84]
Wu, H.J.; Chu, P.Y. Role of cancer stem cells in cholangiocarcinoma and therapeutic implications. Int. J. Mol. Sci., 2019, 20(17), 4154.
[http://dx.doi.org/10.3390/ijms20174154] [PMID: 31450710]
[85]
Govaere, O.; Wouters, J.; Petz, M.; Vandewynckel, Y.P.; Van den Eynde, K.; Van den broeck, A.; Verhulst, S.; Dollé, L.; Gremeaux, L.; Ceulemans, A.; Nevens, F.; van Grunsven, L.A.; Topal, B.; Vankelecom, H.; Giannelli, G.; Van Vlierberghe, H.; Mikulits, W.; Komuta, M.; Roskams, T. Laminin-332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche. J. Hepatol., 2016, 64(3), 609-617.
[http://dx.doi.org/10.1016/j.jhep.2015.11.011] [PMID: 26592953]
[86]
Matlung, H.L.; Szilagyi, K.; Barclay, N.A.; van den Berg, T.K. The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer. Immunol. Rev., 2017, 276(1), 145-164.
[http://dx.doi.org/10.1111/imr.12527] [PMID: 28258703]
[87]
Yang, R.; Wang, D.; Han, S.; Gu, Y.; Li, Z.; Deng, L.; Yin, A.; Gao, Y.; Li, X.; Yu, Y.; Wang, X. MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs. Int. J. Biol. Sci., 2022, 18(1), 43-64.
[http://dx.doi.org/10.7150/ijbs.62602] [PMID: 34975317]
[88]
Qin, X.; Lu, M.; Li, G.; Zhou, Y.; Liu, Z. Downregulation of tumor-derived exosomal miR-34c induces cancer-associated fibroblast activation to promote cholangiocarcinoma progress. Cancer Cell Int., 2021, 21(1), 373.
[http://dx.doi.org/10.1186/s12935-020-01726-6] [PMID: 34261453]
[89]
Luo, C; Xin, H; Zhou, Z; Hu, Z; Sun, R; Yao, N Tumor-derived exosomes induce immunosuppressive macrophages to foster intrahepatic cholangiocarcinoma progression. Hepatology, 2022, 76(4), 982-999.
[http://dx.doi.org/10.1002/hep.32387]
[90]
Sato, K.; Meng, F.; Glaser, S.; Alpini, G. Exosomes in liver pathology. J. Hepatol., 2016, 65(1), 213-221.
[http://dx.doi.org/10.1016/j.jhep.2016.03.004] [PMID: 26988731]
[91]
Ota, Y.; Takahashi, K.; Otake, S.; Tamaki, Y.; Okada, M.; Aso, K.; Makino, Y.; Fujii, S.; Ota, T.; Haneda, M. Extracellular vesicle-encapsulated miR-30e suppresses cholangiocarcinoma cell invasion and migration via inhibiting epithelial-mesenchymal transition. Oncotarget, 2018, 9(23), 16400-16417.
[http://dx.doi.org/10.18632/oncotarget.24711] [PMID: 29662654]
[92]
Li, L.; Piontek, K.; Ishida, M.; Fausther, M.; Dranoff, J.A.; Fu, R.; Mezey, E.; Gould, S.J.; Fordjour, F.K.; Meltzer, S.J.; Sirica, A.E.; Selaru, F.M. Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model. Hepatology, 2017, 65(2), 501-514.
[http://dx.doi.org/10.1002/hep.28735] [PMID: 27474881]
[93]
Sabbatino, F.; Villani, V.; Yearley, J.H.; Deshpande, V.; Cai, L.; Konstantinidis, I.T.; Moon, C.; Nota, S.; Wang, Y.; Al-Sukaini, A.; Zhu, A.X.; Goyal, L.; Ting, D.T.; Bardeesy, N.; Hong, T.S.; Fernandez-del Castillo, C.; Tanabe, K.K.; Lillemoe, K.D.; Ferrone, S.; Ferrone, C.R. PD-L1 and HLA Class I antigen expression and clinical course of the disease in intrahepatic cholangiocarcinoma. Clin. Cancer Res., 2016, 22(2), 470-478.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0715] [PMID: 26373575]
[94]
Qiu, X.; Yang, S.; Wang, S.; Wu, J.; Zheng, B.; Wang, K.; Shen, S.; Jeong, S.; Li, Z.; Zhu, Y.; Wu, T.; Wu, X.; Wu, R.; Liu, W.; Wang, H.Y.; Chen, L. M6A Demethylase ALKBH5 regulates PD-L1 expression and tumor immunoenvironment in intrahepatic cholangiocarcinoma. Cancer Res., 2021, 81(18), 4778-4793.
[http://dx.doi.org/10.1158/0008-5472.CAN-21-0468] [PMID: 34301762]
[95]
Zheng, H.; Zheng, W.; Wang, Z.; Tao, Y.; Huang, Z.; Yang, L.; Ouyang, L.; Duan, Z.; Zhang, Y.; Chen, B.; Xiang, D.; Jin, G.; Fang, L.; Zhou, F.; Liang, B. Decreased expression of programmed death ligand-L1 by seven in absentia homolog 2 in cholangiocarcinoma enhances t-cell–mediated antitumor activity. Front. Immunol., 2022, 13, 845193.
[http://dx.doi.org/10.3389/fimmu.2022.845193] [PMID: 35154166]
[96]
Lin, Y.; Li, B.; Yang, X.; Cai, Q.; Liu, W.; Tian, M.; Luo, H.; Yin, W.; Song, Y.; Shi, Y.; He, R. Fibroblastic FAP promotes intrahepatic cholangiocarcinoma growth via MDSCs recruitment. Neoplasia, 2019, 21(12), 1133-1142.
[http://dx.doi.org/10.1016/j.neo.2019.10.005] [PMID: 31759251]
[97]
Kaushik Dehingia, H.K.S. A brief review on cancer research and its treatment through mathematical modelling. Annals Cancer Res. Thera., 2021, 29(1), 34-40.
[http://dx.doi.org/10.4993/acrt.29.34]
[98]
Chang, L.; Azzolin, L.; Di Biagio, D.; Zanconato, F.; Battilana, G.; Lucon Xiccato, R.; Aragona, M.; Giulitti, S.; Panciera, T.; Gandin, A.; Sigismondo, G.; Krijgsveld, J.; Fassan, M.; Brusatin, G.; Cordenonsi, M.; Piccolo, S. The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. Nature, 2018, 563(7730), 265-269.
[http://dx.doi.org/10.1038/s41586-018-0658-1] [PMID: 30401838]
[99]
Ma, L.; Wang, L.; Khatib, S.A.; Chang, C.W.; Heinrich, S.; Dominguez, D.A.; Forgues, M.; Candia, J.; Hernandez, M.O.; Kelly, M.; Zhao, Y.; Tran, B.; Hernandez, J.M.; Davis, J.L.; Kleiner, D.E.; Wood, B.J.; Greten, T.F.; Wang, X.W. Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J. Hepatol., 2021, 75(6), 1397-1408.
[http://dx.doi.org/10.1016/j.jhep.2021.06.028] [PMID: 34216724]
[100]
Zhou, K.Q.; Liu, W.F.; Yang, L.X.; Sun, Y.F.; Hu, J.; Chen, F.Y.; Zhou, C.; Zhang, X.Y.; Peng, Y.F.; Yu, L.; Zhou, J.; Fan, J.; Wang, Z. Circulating osteopontin per tumor volume as a prognostic biomarker for resectable intrahepatic cholangiocarcinoma. Hepatobiliary Surg. Nutr., 2019, 8(6), 582-596.
[http://dx.doi.org/10.21037/hbsn.2019.03.14] [PMID: 31929985]
[101]
Zheng, Y.; Zhou, C.; Yu, X.X.; Wu, C.; Jia, H.L.; Gao, X.M.; Yang, J.M.; Wang, C.Q.; Luo, Q.; Zhu, Y.; Zhang, Y.; Wei, J.W.; Sheng, Y.Y.; Dong, Q.Z.; Qin, L.X. Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of β-Catenin. Cell Death Dis., 2018, 9(2), 179.
[http://dx.doi.org/10.1038/s41419-017-0226-x] [PMID: 29415992]
[102]
Mandrekar, P.; Cardinale, V. Periostin and mesothelin: Potential predictors of malignant progression in intrahepatic cholangiocarcinoma. Hepatol. Commun., 2018, 2(5), 481-483.
[http://dx.doi.org/10.1002/hep4.1189] [PMID: 29761164]
[103]
Li, D.; Lin, S.; Hong, J.; Ho, M.; Ho, M. Immunotherapy for hepatobiliary cancers: Emerging targets and translational advances. Adv. Cancer Res., 2022, 156, 415-449.
[http://dx.doi.org/10.1016/bs.acr.2022.01.013] [PMID: 35961708]
[104]
Xia, L.; Oyang, L.; Lin, J.; Tan, S.; Han, Y.; Wu, N.; Yi, P.; Tang, L.; Pan, Q.; Rao, S.; Liang, J.; Tang, Y.; Su, M.; Luo, X.; Yang, Y.; Shi, Y.; Wang, H.; Zhou, Y.; Liao, Q. The cancer metabolic reprogramming and immune response. Mol. Cancer, 2021, 20(1), 28.
[http://dx.doi.org/10.1186/s12943-021-01316-8] [PMID: 33546704]
[105]
Hossain, F.; Al-Khami, A.A.; Wyczechowska, D.; Hernandez, C.; Zheng, L.; Reiss, K.; Valle, L.D.; Trillo-Tinoco, J.; Maj, T.; Zou, W.; Rodriguez, P.C.; Ochoa, A.C. Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies. Cancer Immunol. Res., 2015, 3(11), 1236-1247.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0036] [PMID: 26025381]
[106]
Wong, C.C.L.; Tse, A.P.W.; Huang, Y.P.; Zhu, Y.T.; Chiu, D.K.C.; Lai, R.K.H.; Au, S.L.K.; Kai, A.K.L.; Lee, J.M.F.; Wei, L.L.; Tsang, F.H.C.; Lo, R.C.L.; Shi, J.; Zheng, Y.P.; Wong, C.M.; Ng, I.O.L. Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology, 2014, 60(5), 1645-1658.
[http://dx.doi.org/10.1002/hep.27320] [PMID: 25048396]
[107]
Cadamuro, M.; Stecca, T.; Brivio, S.; Mariotti, V.; Fiorotto, R.; Spirli, C.; Strazzabosco, M.; Fabris, L. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochim. Biophys. Acta Mol. Basis Dis., 2018, 1864(4), 1435-1443.
[http://dx.doi.org/10.1016/j.bbadis.2017.07.028] [PMID: 28757170]
[108]
Cekic, C.; Linden, J. Purinergic regulation of the immune system. Nat. Rev. Immunol., 2016, 16(3), 177-192.
[http://dx.doi.org/10.1038/nri.2016.4] [PMID: 26922909]
[109]
Hatfield, S.M.; Kjaergaard, J.; Lukashev, D.; Belikoff, B.; Schreiber, T.H.; Sethumadhavan, S.; Abbott, R.; Philbrook, P.; Thayer, M.; Shujia, D.; Rodig, S.; Kutok, J.L.; Ren, J.; Ohta, A.; Podack, E.R.; Karger, B.; Jackson, E.K.; Sitkovsky, M. Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1α-dependent and extracellular adenosine-mediated tumor protection. J. Mol. Med., 2014, 92(12), 1283-1292.
[http://dx.doi.org/10.1007/s00109-014-1189-3] [PMID: 25120128]
[110]
Ludwig, N.; Yerneni, S.S.; Azambuja, J.H.; Gillespie, D.G.; Menshikova, E.V.; Jackson, E.K.; Whiteside, T.L. Tumor-derived exosomes promote angiogenesis via adenosine A2B receptor signaling. Angiogenesis, 2020, 23(4), 599-610.
[http://dx.doi.org/10.1007/s10456-020-09728-8] [PMID: 32419057]
[111]
Nguyen-Lefebvre, A.T.; Selzner, N.; Wrana, J.L.; Bhat, M. The hippo pathway: A master regulator of liver metabolism, regeneration, and disease. FASEB J., 2021, 35(5), e21570.
[http://dx.doi.org/10.1096/fj.202002284RR] [PMID: 33831275]
[112]
Marzagalli, M.; Ebelt, N.D.; Manuel, E.R. Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment. Semin. Cancer Biol., 2019, 59, 236-250.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.002] [PMID: 31404607]
[113]
Lin, C.; Xu, X. YAP1-TEAD1-Glut1 axis dictates the oncogenic phenotypes of breast cancer cells by modulating glycolysis. Biomed. Pharmacother., 2017, 95, 789-794.
[http://dx.doi.org/10.1016/j.biopha.2017.08.091] [PMID: 28892790]
[114]
Zimmerman, R.; Fogt, F.; Burke, M.; Murakata, L. Assessment of Glut-1 expression in cholangiocarcinoma, benign biliary lesions and hepatocellular carcinoma. Oncol. Rep., 2002, 9(4), 689-692.
[http://dx.doi.org/10.3892/or.9.4.689] [PMID: 12066193]
[115]
Di Matteo, S.; Nevi, L.; Overi, D.; Landolina, N.; Faccioli, J.; Giulitti, F.; Napoletano, C.; Oddi, A.; Marziani, A.M.; Costantini, D.; De Rose, A.M.; Melandro, F.; Bragazzi, M.C.; Grazi, G.L.; Berloco, P.B.; Giuliante, F.; Donato, G.; Moretta, L.; Carpino, G.; Cardinale, V.; Gaudio, E.; Alvaro, D. Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells. Sci. Rep., 2021, 11(1), 2557.
[http://dx.doi.org/10.1038/s41598-021-81172-0] [PMID: 33510179]
[116]
Choi, H.; Na, K.J. Different glucose metabolic features according to cancer and immune cells in the tumor microenvironment. Front. Oncol., 2021, 11, 769393.
[http://dx.doi.org/10.3389/fonc.2021.769393] [PMID: 34966676]
[117]
Labib, P.L.; Goodchild, G.; Pereira, S.P. Molecular pathogenesis of cholangiocarcinoma. BMC Cancer, 2019, 19(1), 185.
[http://dx.doi.org/10.1186/s12885-019-5391-0] [PMID: 30819129]
[118]
Yang, H.; Ye, D.; Guan, K.L.; Xiong, Y. IDH1 and IDH2 mutations in tumorigenesis: Mechanistic insights and clinical perspectives. Clin. Cancer Res., 2012, 18(20), 5562-5571.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1773] [PMID: 23071358]
[119]
Ruiz de Gauna, M.; Biancaniello, F.; González-Romero, F.; Rodrigues, P.M.; Lapitz, A.; Gómez-Santos, B.; Olaizola, P.; Di Matteo, S.; Aurrekoetxea, I.; Labiano, I.; Nieva-Zuluaga, A.; Benito-Vicente, A.; Perugorria, M.J.; Apodaka-Biguri, M.; Paiva, N.A.; Sáenz de Urturi, D.; Buqué, X.; Delgado, I.; Martín, C.; Azkargorta, M.; Elortza, F.; Calvisi, D.F.; Andersen, J.B.; Alvaro, D.; Cardinale, V.; Bujanda, L.; Banales, J.M.; Aspichueta, P. Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids. Hepatology, 2022, 76(6), 1617-1633.
[http://dx.doi.org/10.1002/hep.32344] [PMID: 35030285]
[120]
Dehingia, K.; Yao, S.W.; Sadri, K.; Das, A.; Sarmah, H.K.; Zeb, A.; Inc, M. A study on cancer-obesity-treatment model with quadratic optimal control approach for better outcomes. Results Phys., 2022, 42, 105963.
[http://dx.doi.org/10.1016/j.rinp.2022.105963]
[121]
Dehingia, K.; Sarmah, H.K.; Hosseini, K.; Sadri, K.; Salahshour, S.; Park, C. An optimal control problem of immuno-chemotherapy in presence of gene therapy. AIMS Mathematics, 2021, 6(10), 11530-11549.
[http://dx.doi.org/10.3934/math.2021669]

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