Abstract
During the past decade, a better understanding of the cellular and molecular mechanisms underlying tumor immunity has provided the appropriate framework for the development of therapeutic strategies for cancer immunotherapy. Under this complex scenario, galectins have emerged as promising molecular targets for cancer therapy responsible of creating immunosuppressive microenvironments at sites of tumor growth and metastasis. Galectins, expressed in tumor, stromal, and endothelial cells, contribute to thwart the development of immune responses by favoring the expansion of T regulatory cells and contributing to their immunosuppressive activity, driving the differentiation of tolerogenic dendritic cells, limiting T cell viability, and maintaining T cell anergy. The emerging data promise a future scenario in which the selective blockade of individual members of the galectin family, either alone or in combination with other therapeutic regimens, will contribute to halt tumor progression by counteracting tumor-immune escape. Here we describe a selection of methods used to investigate the role of galectin-1 in tumor-immune escape.
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References
Drake CG, Jaffee E, Pardoll DM (2006) Mechanisms of immune evasion by tumors. Adv Immunol 90:51–81
Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296
Antonopoulos A, North SJ, Haslam SM, Dell A (2011) Glycosylation of mouse and human immune cells: insights emerging from N-glycomics analyses. Biochem Soc Trans 39:1334–1340
Rabinovich GA, van Kooyk Y, Cobb BA (2012) Glycobiology of immune responses. Ann N Y Acad Sci 1253:1–15
Hakomori SI, Cummings RD (2012) Glycosylation effects on cancer development. Glycoconj J 29:565–566
Rabinovich GA, Croci DO (2012) Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 36:322–335
Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5:29–41
Toscano MA et al (2007) Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8:825–834
Ilarregui JM et al (2009) Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol 10:981–991
Barrionuevo P et al (2007) A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol 178:436–445
Starossom SC et al (2012) Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity 37:249–263
He J, Baum LG (2006) Galectin interactions with extracellular matrix and effects on cellular function. Methods Enzymol 417:247–256
Cooper D et al (2010) Multiple functional targets of the immunoregulatory activity of galectin-1: control of immune cell trafficking, dendritic cell physiology, and T-cell fate. Methods Enzymol 480:199–244
Dalotto-Moreno T et al (2013) Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res 73:1107–1117
Cedeno-Laurent F, Opperman M, Barthel SR, Kuchroo VK, Dimitroff CJ (2012) Galectin-1 triggers an immunoregulatory signature in Th cells functionally defined by IL-10 expression. J Immunol 188:3127–3137
Saussez S et al (2007) High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas. Int J Oncol 30:1109–1117
Laderach DJ et al (2013) A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Res 73:86–96
Hittelet A et al (2003) Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration. Int J Cancer 103:370–379
Sanjuan X et al (1997) Differential expression of galectin 3 and galectin 1 in colorectal cancer progression. Gastroenterology 113:1906–1915
van den Brule F et al (2003) Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Lab Invest 83:377–386
Kim HJ et al (2012) High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion. Eur J Cancer 48:1914–1921
Jung EJ et al (2007) Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer 120:2331–2338
Rubinstein N et al (2004) Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; a potential mechanism of tumor-immune privilege. Cancer Cell 5:241–251
Kamper P et al (2011) Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma. Blood 117:6638–6649
Ouyang J et al (2013) Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood 121(17):3431–3433
Kim HJ et al (2013) Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer. Hum Pathol 44:62–68
Zacarias Fluck MF et al (2012) The aggressiveness of murine lymphomas selected in vivo by growth rate correlates with galectin-1 expression and response to cyclophosphamide. Cancer Immunol Immunother 61:469–480
Tang D et al (2012) High expression of Galectin-1 in pancreatic stellate cells plays a role in the development and maintenance of an immunosuppressive microenvironment in pancreatic cancer. Int J Cancer 130:2337–2348
Soldati R et al (2012) Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments. Int J Cancer 131(5):1131–1141
Espelt MV et al (2011) Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth. Hepatology 53:2097–2106
Wu H et al (2012) Overexpression of galectin-1 is associated with poor prognosis in human hepatocellular carcinoma following resection. J Gastroenterol Hepatol 27:1312–1319
Croci DO et al (2013) Nurse-like cells control the activity of chronic lymphocytic leukemia B cells via galectin-1. Leukemia 27(6):1413–1416
Camby I et al (2001) Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration. Brain Pathol 11:12–26
Strik HM et al (2007) Galectin-1 expression in human glioma cells: modulation by ionizing radiation and effects on tumor cell proliferation and migration. Oncol Rep 18:483–488
Juszczynski P et al (2010) MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1. Clin Cancer Res 16:2122–2130
Saussez S et al (2008) Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid 18:705–712
Salatino M, Rabinovich GA (2011) Fine-tuning antitumor responses through the control of galectin-glycan interactions: an overview. Methods Mol Biol 677:355–374
Ito K, Ralph SJ (2012) Inhibiting galectin-1 reduces murine lung metastasis with increased CD4(+) and CD8 (+) T cells and reduced cancer cell adherence. Clin Exp Metastasis 29(6):561–572
Juszczynski P et al (2007) The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A 104:13134–13139
Kuo PL et al (2012) Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor. J Biol Chem 287:9753–9764
Demotte N et al (2010) A galectin-3 ligand corrects the impaired function of human CD4 and CD8 tumor-infiltrating lymphocytes and favors tumor rejection in mice. Cancer Res 70:7476–7488
Peng W, Wang HY, Miyahara Y, Peng G, Wang RF (2008) Tumor-associated galectin-3 modulates the function of tumor-reactive T cells. Cancer Res 68:7228–7236
Dardalhon V et al (2010) Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b + Ly-6G + myeloid cells. J Immunol 185:1383–1392
Tsuboi S et al (2011) A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J 30:3173–3185
Yamaguchi T et al (2007) Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27:145–159
Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T (2009) Regulatory T cells: how do they suppress immune responses? Int Immunol 21:1105–1111
Wiznerowicz M, Trono D (2003) Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference. J Virol 77:8957–8961
Rabinovich GA et al (2006) Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology 16:210–220
Toscano MA et al (2007) Dissecting the pathophysiologic role of endogenous lectins: glycan-binding proteins with cytokine-like activity? Cytokine Growth Factor Rev 18:57–71
Acknowledgements
Work in our laboratory is supported by grants from The Argentinean Agency for Promotion of Science and Technology (G.A.R, M.S., D.J.L, M.A.T, D.C.), University of Buenos Aires (G.A.R), Prostate Cancer Action (G.A.R., D.J.L, D.C), Argentinean Council of Scientific and Technical Investigations (M.S), National Multiple Sclerosis Society (G.A.R.), Broad Foundation (G.A.R.), and Sales Foundation (G.A.R).
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Cerliani, J.P. et al. (2015). Study of Galectins in Tumor Immunity: Strategies and Methods. In: Stowell, S., Cummings, R. (eds) Galectins. Methods in Molecular Biology, vol 1207. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1396-1_16
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DOI: https://doi.org/10.1007/978-1-4939-1396-1_16
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