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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. Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Compagno, Daniel Georges. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Laderach, Diego Jose. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gentilini, Lucas Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

Galectin-1 (Gal1), a β-galactoside-binding protein abundantly expressed in tumor microenvironments, is associated with the development of metastasis in hepatocellular carcinomas (HCC). However, the precise roles of Gal1 in HCC cell invasiveness and dissemination are uncertain. Here, we investigated whether Gal1 mediate epithelial mesenchymal transition (EMT) in HCC cells, a key process during cancer progression. We used the well-differentiated and low invasive HepG2 cells and performed ?gain-of-function? and ?loss-function? experiments by transfecting cells with Gal1 cDNA constructs or by siRNA strategies, respectively. Epithelial and mesenchymal markers expression, changes in apico basal polarity, independent-anchorage growth and activation of specific signaling pathways were studied using Western blot, fluorescence microscopy, soft-agar assays and FOP/TOP flash reporter system. Gal1 up-regulation in HepG2 cells induced down-regulation of the adherens junction protein E-cadherin and increased expression of the transcription factor Snail, one of the main inducers of EMT in HCC. Enhanced Gal1 expression facilitated the transition from epithelial cell morphology towards a fibroblastoid phenotype and favored up regulation of the mesenchymal marker vimentin in HCC cells. Cells overexpressing Gal1 showed enhanced anchorage-independent growth and loss of apico-basal polarity.Remarkably, Gal1 promoted Akt activation, β-catenin nuclear translocation, TCF4/LEF1 transcriptional activity and increased cyclin D1 and c-Myc expression, suggesting activation of the Wnt pathway. Furthermore, Gal1 overexpression induced E-cadherin downregulation through a PI3K/Akt-dependent mechanism. Our results provide the first evidence of a role of Gal1 as an inducer of EMT in HCC cells, with critical implications in HCC metastasis. Fil: Bacigalupo, Maria Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Espelt, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Gentilini, Lucas Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Compagno, Daniel Georges. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Laderach, Diego Jose. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Wolfenstein, Carlota Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Troncoso, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina

Although blocking vascular endothelial growth factor (VEGF) signaling is clinically beneficial in certain cancers, tumor regrowth in treated patients suggests that compensatory angiogenic programs may limit the efficacy of anti-VEGF treatment. We found that association of galectin-1 with complex N-glycans on VEGFR2 links tumor hypoxia to VEGFR2 signaling and preserves angiogenesis in response to VEGF blockade. Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

Al producirse una lesión de médula espinal (LME), un sinnúmero de proteínas inhibidoras de la regeneración axonal ocupan el sitio de lesión en forma secuencial. La primer proteína en llegar al mismo se conoce como semaforina 3A (Sema3A), siendo además una de las más potentes por su acción de inhibir la regeneración axonal. A nivel mecanístico la unión de esta proteína al complejo-receptor neuronal neuropilin-1 (NRP-1)/PlexinA4 evita que se produzca regeneración axonal. En este trabajo de revisión se discutirá la acción de galectin-1 (Gal-1), una proteína endógena de unión a glicanos, que selectivamente se une al complejo-receptor NRP-1/PlexinA4 de las neuronas lesionadas a través de un mecanismo dependiente de interacciones lectina-glicano, interrumpiendo la señalización generada por Sema3A y permitiendo de esta manera la regeneración axonal y recuperación locomotora luego de producirse la LME. Mientras ambas formas de Gal-1 (monomérica y dimérica) contribuyen a la inactivación de la microglia, solo la forma dimérica de Gal-1 es capaz deunirse al complejo-receptor NRP-1/PlexinA4 y promover regeneración axonal. Por lo tanto, Gal-1 dimérica produce recuperación de las lesiones espinales interfiriendo en la señalización de Sema3A a través de la unión al complejoreceptor NRP-1/PlexinA4, sugiriendo el uso de esta lectina en su forma dimérica para el tratamiento de pacientes con LME. When spinal cord injury (SCI) occurs, a great number of inhibitors of axonal regeneration consecutively invade the injured site. The first protein to reach the lesion is known as semaphorin 3A (Sema3A), which serves as a powerful inhibitor of axonal regeneration. Mechanistically binding of Sem3A to the neuronal receptor complex neuropilin-1 (NRP1) / PlexinA4 prevents axonal regeneration. In this special article we review the effects of galectin-1 (Gal-1), an endogenous glycan-binding protein, abundantly present at inflammation and injury sites. Notably, Gal1 adheres selectively to the NRP-1/PlexinA4 receptor complex in injured neurons through glycan-dependent mechanisms, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. While both the monomeric and dimeric forms of Gal-1 contribute to ’switch-off’ classically-activated microglia, only dimeric Gal-1 binds to the NRP-1/PlexinA4 receptor complex and promotes axonal regeneration. Thus, dimeric Gal-1 promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A adhering to the NRP-1/PlexinA4 complex, supporting the use of dimeric Gal-1 for the treatment of SCI patients. Fil: Quintá, Héctor Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina

Galectin-8 (Gal-8) is a ´tandem-repeat´-type galectin, which possesses two carbohydrate recognition domains connected by a linker peptide. Gal-8 complexity is related to the alternative splicing of its mRNA precursor, which is known to generate isoforms. Regarding its carbohydrate-binding specificity, Gal-8 has a unique feature among galectins, since its C-terminal domain has higher affinity for N-glycan-type branched oligosaccharides, while its N-terminal domain shows strong affinity for α2-3-sialylated or 3´-sulfated β-galactosides. We integrate here the available information on Gal-8 expression in different tumor types and attempt to elucidate associations of its expression and localization with tumor progression with the overarching goal of analyzing its potential applications in diagnosis and prognosis. Differential diagnosis is still a prime concern in tumor pathology, and Gal-8 could be of great value in some types of primary or secondary tumors (i.e. papillary thyroid carcinoma, advanced colon carcinoma from patients with distant metastases, or metastases from primary lung carcinoma). The prognostic value of Gal-8 has been described for laryngeal carcinoma as well as advanced colon carcinoma. Further studies are needed to explain the relevance of Gal-8 and its isoforms in tumor pathology and their different intra- or extracellular roles (cytoplasmic, nuclear or extracellular) in tumor biology. Fil: Elola, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Ferragut, Fatima Eneida del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Cardenas Delgado, Victor Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Nugnes, Lorena Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Gentilini, Lucas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Laderach, Diego Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Troncoso, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Compagno, Daniel Georges. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Wolfenstein, Carlota Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Hepatocellular carcinoma (HCC) represents a global health problem. Infections with hepatitis B or C virus, non-alcoholic steatohepatitis disease, alcohol abuse, or dietary exposure to aflatoxin are the major risk factors to the development of this tumor. Regardless of the carcinogenic insult, HCC usually develops in a context of cirrhosis due to chronic inflammation and advanced fibrosis. Galectins are a family of evolutionarily-conserved proteins defined by at least one carbohydrate recognition domain with affinity for β-galactosides and conserved sequence motifs. Here, we summarize the current literature implicating galectins in the pathogenesis of HCC. Expression of ?proto-type? galectin-1, ?chimera- type? galectin-3 and ?tandem repeat-type? galectin- 4 is up-regulated in HCC cells compared to their normal counterparts. On the other hand, the ?tandemrepeat- type? lectins galectin-8 and galectin-9 are downregulated in tumor hepatocytes. The abnormal expression of these galectins correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, postoperative recurrence and poor prognosis. Moreover, these galectins have important roles in other pathological conditions of the liver, where chronic inflammation and/or fibrosis take place. Galectin-based therapies have been proposed to attenuate liver pathologies. Further functional studies are required to delineate the precise molecular mechanisms through which galectins contribute to HCC. Fil: Bacigalupo, Maria Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina; Fil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina; Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biologia y Medicina Experimental (i); Argentina; Fil: Troncoso, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina

Galectin-3, an endogenous glycan-binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. However, the role of galectin-3 within the CD4+CD25+Foxp3+ T regulatory (TREG) cell compartment has not yet been explored. Here, we found, in a model of Leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral TREG cells both in draining lymph nodes (LNs) and sites of infection. These observations correlated with an increased severity of the disease, as shown by increased footpad swelling and parasite burden. Galectin-3-deficient (Lgals3−/−) TREG cells displayed higher CD103 expression, showed greater suppressive capacity, and synthesized higher amounts of IL-10 compared with their wild-type (WT) counterpart. Furthermore, both TREG cells and T effector (TEFF) cells from Lgals3−/− mice showed higher expression of Notch1 and the Notch target gene Hes-1. Interestingly, Notch signaling components were also altered in both TREG and TEFF cells from uninfected Lgals3−/− mice. Thus, endogenous galectin-3 regulates the frequency and function of CD4+CD25+Foxp3+ TREG cells and alters the course of L. major infection. Fil: Fermino, Marise L.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Fil: Dias, Fabrício C.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Fil: Lopes, Carla D.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Fil: Souza, Maria A.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Universidade Federal de Uberlândia. Instituto de Ciências Biomédicas. Departamento de Imunologia; Brasil; Fil: Cruz, Ângela K.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Fil: Liu, Fu Tong. University of California Davis. School of Medicine. Department of Dermatology; Estados Unidos de Amèrica; Fil: Chammas, Roger. Universidade de São Paulo. Faculdade de Medicina. Departamento de Radiologia e Oncologia; Brasil; Cancer Institute of the State of Sao Paulo. Center for Translational Research in Oncology; Brasil; Fil: Roque Barreira, Maria C.. Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular; Brasil; Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina; Fil: Bernardes, Emerson S.. Universidade de São Paulo. Faculdade de Medicina. Departamento de Radiologia e Oncologia; Brasil; Cancer Institute of the State of Sao Paulo. Center for Translational Research in Oncology; Brasil

Successful mammalian pregnancy relies upon acceptance of a semi-allogeneic fetus by the maternal immune system. Lessons learned from studies on protective immunity to microbial infections and tumours, prevention of autoimmunity, and allograft rejection have contributed to delineate the mechanisms leading to T-cell tolerance at the fetomaternal interface. Recent observations highlight the contribution of galectins, a family of endogenous glycan-binding proteins, to critical biological events occurring during mammalian gestation, including immune cell tolerance, inflammation, implantation, and angiogenesis. These multifunctional lectins can hierarchically control a cascade of immunoregulatory events including the expansion, recruitment, and function of regulatory T cells, the promotion of tolerogenic dendritic cells, and the execution of T-cell death programs. In addition, galectins can control cell adhesion and signaling events critical for implantation and are involved in fundamental processes linking tissue hypoxia to angiogenesis. In an attempt to integrate the regulatory roles of galectins to immunological and vascular programs operating during pregnancy. Here we outline the regulated expression and function of individual members of the galectin family within the fetoplacental unit and their biological implications for the development and preservation of successful pregnancies. © 2013 John Wiley & Sons A/S. Fil: Blidner, Ada Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors. Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Rubinstein, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Cavallin, Lucas E.. Miami University; Estados Unidos Fil: Leung, Howard J.. Miami University; Estados Unidos Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos Fil: Ilarregui, Juan Martin. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Croci, María C.. Universidad Nacional del Comahue; Argentina Fil: Shipp, Margaret A.. Dana Farber Cancer Institute; Estados Unidos Fil: Mesri, Enrique A.. Miami University; Estados Unidos Fil: Albini, Adriana. Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica; Italia Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

Las galectinas, una familia de lectinas que reconocen glico-conjugados específicos en la superficie celular y la matriz, participan en diversos procesos biológicos como reguladores de la ho-meostasis de la respuesta inmune y de la progresión tumoral. Considerando el papel inmunomodulador de Galectina-1 (Gal-1) en modelos de inflamación crónica y su contribución a la creación de microambientes tolerogénicos, durante los últimos años exploramos el impacto de esta proteína sobre el balance de células T y la funcionalidad de células dendríticas (CDs). Mientras las células Th1 y Th17 poseen el repertorio de glicanos necesarios para la unión de Gal-1, los linfocitos Th2 son resistentes a la unión de esta proteína, lo cual explicaría el incremento en la susceptibilidad de los linfocitos Th1 y Th17 a la apoptosis inducida por Gal-1 y la consecuente desviación en el balance de la respuesta inmune hacia un perfil Th2. Además, identificamos un circuito tolerogénico en el que Gal‐1 induce la diferenciación de CDs tolerogénicas productoras de IL‐27, la consecuente expansión de células T regulatorias productoras de IL‐10 y la supresión de la inflamación mediada por células Th1 y Th17. Postulamos un nuevo mecanismo de regulación homeostática de la respuesta inmune basado en la interacción entre Gal‐1 y sus gli-canos específicos, el cual permite anticipar nuevos horizontes terapéuticos, en los que la modulación de la expresión de Gal‐1 o sus glicanos nos permitiría regular la respuesta inmune. Galectins, a family of endogenous glycan-binding proteins able to recognize specific glycoconjugates on cell surface and extracellular matrix, control critical immunological processes involved in immune homeostasis and tumor progression. Given the immunosuppressive role of Galectin-1 (Gal-1) in different models of chronic inflammation and its contribution to the creation of tolerogenic microenvironments in cancer and pregnancy models, the impact of this protein on T helper cell balance and dendritic cells (DCs) functionality was explored. A novel mechanism, based on the differential glycosylation of T helper cell subsets, by which Gal-1 preferentially eliminates antigen-specific Th1 and Th17 cells, leading to a shift toward a Th2 profile was identified. While Th1- and Th-17-differentiated cells expressed the repertoire of cell surface glycans that are critical for Gal-1-induced cell death, Th2 cells are protected from Gal-1 through differential sialylation of cell surface glycoproteins. More recently, the ability of Gal-1 to trigger the differentiation of tolerogenic dendritic cells (DCs), which promote resolution of autoimmune inflammation, was demonstrated. A tolerogenic circuit linking Gal-1 signaling, IL-27-producing DCs and IL-10-secreting T cells was identified. It can be postulated that molecular interactions between endogenous galectins and specific glycans constitute a novel mechanism of homeostatic regulation of immune responses. Understanding the role of protein-glycan interactions in the establishment of tolerogenic or inflammatory programs will enable the design of more rational immunotherapeutic strategies with broad biomedical implications. As galectinas, uma família de lectinas que reconhecem gli-coconjugados específicos na superfície celular e a matriz, participam em diversos processos biológicos como reguladores da homeostase da resposta imune e da progressão tu-moral. Considerando o papel imunomodulador de Galec-tina-1 (Gal-1) em modelos de inflamação crônica e sua contribuição à criação de microambientes tolerogênicos, durante os últimos anos exploramos o impacto desta proteína sobre o balanço de células T e a funcionalidade de células dendríticas (CDs). Enquanto as células Th1 e Th17 possuem o repertório de glicanos necessários para a união de Gal-1, os linfócitos Th2 são resistentes à união desta proteína, o qual explicaria o incremento na suscetibilidade dos linfóci-tos Th1 e Th17 à apoptose induzida por Gal-1 e o conse-guinte desvio no balanço da resposta imune para um perfil Th2. Além disso, identificamos um circuito tolerogênico no qual Gal‐1 induz a diferenciação de CDs tolerogênicas pro-dutoras de IL‐27, a conseguinte expansão de células T re-gulatórias produtoras de IL‐10 e a supressão da inflamação mediada por células Th1 e Th17. Postulamos um novo mecanismo de regulação homeostática da resposta imune ba-seado na interação entre Gal‐1 e seus glicanos específicos, que permite antecipar novos horizontes terapêuticos, nos quais a modulação da expressão de Gal‐1 ou seus glicanos nos permitiria regular a resposta imune. Fil: Sundblad, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Compagno, Daniel Georges. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Di Lella, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Gatto, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Gentilini, Lucas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Giribaldi, María Laura. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Laboratorio de Analisis Biologicos E Inmunoquimica; Argentina Fil: Guardia, Carlos Manuel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Laderach, Diego Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Martínez Allo, Verónica Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina

Tumors may usurp certain mediators and signaling pathways used by normal cells to evade or shift immune responses (1). Unlocking these mechanisms may help the implementation of novel therapeutic approaches in cancer patients. Two independent studies published in the March issue of Journal of Experimental Medicine (1,2) show that thymic stromal lymphopoietin (TSLP), an IL-7-related cytokine abundant in the tumor microenvironment, instructs dendritic cells (DCs) to shift the balance toward Th2-mediated inflammatory responses that incite and sustain tumor progression. Fil: Laderach, Diego Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Pesoa, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Compagno, Daniel Georges. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

This March nearly 150 investigators attended the first international meeting focused solely on the role of glycans within the immune system. This Keystone Symposia meeting entitled “New Frontiers at the Interface of Immunity and Glycobiology” took place at Lake Louise, Alberta, Canada and was organized by Brian Cobb, Gabriel Rabinovich, and Yvette van Kooyk. We are pleased to report that the state of this union is strong and growing. “Glycoimmunology” includes both the immunology and glycobiology communities and is a rapidly expanding field as the involvement of carbohydrates in host responses rises to prominence. This growing awareness is visible within the Consortium for Functional Glycomics, led by the meeting's keynote speaker Jim Paulson of the Scripps Research Institute in La Jolla, CA, in which more than half of the 540 participating investigators have a stated interest in understanding the role of glycans and glycan-binding proteins within the immune system. Although the society-oriented meetings for glycobiology and immunology do touch on some of the areas of convergence, it is clear that they do not adequately cover the diverse areas of active investigation at this interface. As a result, the two underlying goals of this meeting were to bring those investigators together to better define the glycoimmunology field and to raise awareness of the importance of glycans in the immune system. Fil: Cobb, Brian. Case Western Reserve University; Estados Unidos Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Van Kooyk, Yvette. VU University Medical Center; Países Bajos

Galectin-3 belongs to a family of highly conserved animal lectins characterized by their ability to recognize multiple N-acetyllactosamine sequences, which can be displayed on both N- and O-glycans on cell surface glycoconjugates. Although first identified in macrophages, galectin-3 (also called "Mac-2, εBP, CBP35 or L-29") has been found to be widely distributed in several tissues and developmental stages where, depending on its extracellular or intracellular localization, it can display a broad diversity of biological functions including immunomodulation, host-pathogen interactions, embryogenesis, angiogenesis, cell migration, wound healing and apoptosis. In spite of the existence of several reviews describing the multifunctional properties of galectin-3, an integrated view of the regulated expression of this glycan-binding protein in different normal tissues is lacking. Here we attempt to summarize and integrate available information on galectin-3 distribution in normal haematopoietic and non-haematopoietic tissues, mainly in adulthood, with only a brief reference to its expression during embryonic stages. In addition, given the multiplicity of biological roles attributed to this protein, a brief description of galectin-3 functions is also included. Understanding how galectin-3 is regulated in normal tissues will contribute to a rational design of approaches aimed at modulating galectin-3 expression and subcellular localization for experimental and therapeutic purposes. Fil: Sundblad, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

In recent years, we have witnessed critical advances in genomics and proteomics which contributed to delineate the "tumor progression signature". This includes the altered expression of genes and proteins not only in tumor cells, but also in tumor-associated stromal, endothelial, and immune cells. Adding more complexity to this bewildering information, efforts are being made to define the "glycosylation signature" of the tumor microenvironment, which results from the abnormal expression and activity of glycosyltransferases, glycosidases, and enzyme chaperons. The multiple combinatorial possibilities of glycan structures expressed by neoplastic versus normal tissue provide enormous potential for information display and expand potential therapeutic opportunities. The responsibility of deciphering the biological information encoded by the tumor-associated glycome is partially assigned, to distinct families of endogenous glycan-binding proteins or lectins, whose expression and function are regulated in cancerous tissues. Galectins, a family of evolutionarily conserved glycan-binding proteins, can control tumor progression by directly influencing tumor growth or by modulating cell migration, angiogenesis, and tumor-immune escape. In this review, we will highlight recent findings on how galectin-glycan lattices control the dialogue between tumor and immune cells and how these interactions could be exploited for therapeutic purposes. Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

In the postgenomic era, the study of the glycome- the whole repertoire of saccharides in cells and tissues- has enabled the association of unique glycan structures with specific physiological and pathological processes. The responsability for deciphering this biological information belongs to endogenous glycan-binding proteins or lectins. Galectin-1, a prototype member of a family of structurally-related proteins, has demonstrated selective antiinflammatory and immunoregulatory effects either by controlling immune cell trafficking, fine-tuning dendritic cell physiology and regulating T cell phate. These regulatory functions mediated by an endogenous glycan-binding protein may contribute tuo fullfil the needs for immune cell homeostasis. Fil: Cooper, Dianne. Queen Mary University of London. The William Harvey Research Institute; Reino Unido Fil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Queen Mary University of London. The William Harvey Research Institute; Reino Unido Fil: Pesoa, Susana A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina Fil: Perretti, Mauro. Queen Mary University of London. The William Harvey Research Institute; Reino Unido Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

B-galactoside-binding animal lectins, are differentially expressed by various immune cells, as well as a wide range of other cell types. Extracellularly, they are able to exhibit bivalent or multivalent interactions with cell surface glycans on various immune cells and exert various effects. These include cytokine and mediator production, cell adhesion, apoptosis, and chemoattraction. In addition, they can form lattices with cell surface glycoprotein receptors, resulting in modulation of receptor functions including clustering and endocytosis. Intracellularly, galectins can participate in signaling pathways and modulate biological responses. These include apoptosis, cell differentiation and cell migration. Thus, a large body of literature indicates that galectins play important roles in the immune and inflammatory responses through regulating the homeostasis and functions of immune cells. The use of mice deficient in individual galectins has provided additional evidence for these proteins’ contributions to these responses. Current research indicates that galectins play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies, autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus, recombinant proteins or specific galectin inhibitors may be employed as therapeutic agents for inflammatory diseases. Fil: Liu, Fu-Tong . University Of California At Davis; Estados Unidos Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina