ONCO-IMMUNOLOGY
The Laboratory of Onco-immunology is focused on studying chronic B cell neoplasms, particularly chronic lymphocytic leukemia (CLL). Leukemic cells from CLL patients recirculate between the blood and lymphoid organs where they receive pro-survival signals from the protective microenvironment, leading to progression and resistance to antineoplastic therapy. On the other hand, leukemic cells induce the dysregulation of both, innate and adaptative immunity, through the release of soluble factors and cell-to-cell contact. The aim of the laboratory is to investigate the regulatory mechanisms of CLL migration, the characteristic immunodeficiency of CLL patients and the role of novel agents (kinase inhibitors and BCL-2 inhibitors) on non-malignant leukocytes. Throughout the years we have established collaborations with different public and private health institutions which have favored and improved the translational aims of our research. The incorporation of the CLL murine model, the Eµ-TCL1, into the IMEX animal facility has widened the possibilities of investigation, particularly those which implicate infectious agents or the evaluation of novel therapeutic strategies.
Chair: Mirta Giordano, PhD.
CONICET Senior investigator
E-mail: giordanomirta@gmail.com
Co-Chair: Romina Gamberale, PhD.
CONICET Independent researcher.
E-mail: rominagamberale@gmail.com
- Mercedes Borge, PhD. CONICET Associate researcher .
E-mail: mercedesborge@hotmail.com
- Pablo Morande, PhD. CONICET Assistant researcher.
E-mail: pabloemorande@gmail.com
- Ana Colado, PhD. Postdoctoral student – CONICET. Supervisor: Mercedes Borge, PhD
- Valeria Sarapura Martínez, MD. Doctoral student. Supervisor: Romina Gamberale, PhD
- Gregorio Cordini, MD. Doctoral student. Supervisor: Romina Gamberale, PhD
- Lic. Chiara Cassarino, Doctoral student. Supervisor: Mercedes Borge, PhD
Novel therapeutic agents in hematologic neoplasms.
Aim: to characterize phenotypic and functional changes induced by target agents (kinase inhibitors and BCL-2 inhibitors) in innate immune cells from patients with B cell neoplasms and in Eµ-TCL1 mice.
Role of sphingosine kinases in CLL.
Aim: to analyze the expression and function of sphingosine kinases in CLL cells and the effect of specific inhibitors in survival, activation and proliferation of leukemic clone.
Role of GRK2 in CLL.
Aim: to study the implication of GRK2 and the S1P/S1PR1 axis in the migration and homing of CLL cells to secondary lymphoid organs, their relevance to disease progression and resistance to therapeutic agents.
Immunomodulatory effects of Igs in CLL.
Aim: to determine the regulatory capacity of Igs, both endogenous and therapeutic (IVIg for patients with hypogammaglobulinemia), in the activation and survival of CLL cells and non-malignant leukocytes from the tumoral microenvironment.
- Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia. Valeria J Sarapura Martinez, Brenda Buonincontro, Chiara Cassarino, Juliana Bernatowiez, Ana Colado, Gregorio Cordini, Maria del Rosario Custidiano, Carolina Mahuad, Miguel A. Pavlovsky, Raimundo F. Bezares, Nicolás Octavio Favale, Mónica Vermeulen, Mercedes Borge, Mirta Giordano and Romina Gamberale. Frontiers in Oncology 2023 Mar 20;13:1143881. doi: 10.3389/fonc.2023.1143881. eCollection 2023.
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives. Gargiulo E, Giordano M, Niemann CU, Moussay E, Paggetti J, Morande PE. Front Oncol. 2023 Mar 8;13:1122699. doi: 10.3389/fonc.2023.1122699. eCollection 2023.
- Venetoclax-resistant CLL cells show a highly activated and proliferative phenotype. Elias EE, Sarapura Martinez VJ, Amondarain M, Colado A, Cordini G, Bezares RF, Fernandez Grecco H, Custidiano MDR, Sánchez Ávalos JC, Garate G, Pavlovsky MA, Borge M, Giordano M, Gamberale R. Cancer Immunol Immunother. 2022 Apr;71(4):979-987. doi: 10.1007/s00262-021-03043-x.
- COVID-19 Vaccination Responses with Different Vaccine Platforms in Patients with Inborn Errors of Immunity. L Erra, I Uriarte, A Colado, MV Paolini, G Seminario , J Belén Fernández, L Tau, J Bernatowiez, I Moreira, S Vishnopolska, M Rumbo, C Cassarino, G Vijoditz, AL López, R Curciarello, D Rodríguez, G Rizzo, M Ferreyra, L Ferreyra Mufarregue, MN Badano, MI Pérez Millán, MF Quiroga, P Baré, I Ibañez, R Pozner, M Borge, G Docena, L Bezrodnik, MB Almejun. J Clin Immunol. 2022 Oct 17;1-15. doi: 10.1007/s10875-022-01382-7.
- In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia. Vereertbrugghen A, Colado A, Gargiulo E, Bezares RF, Fernández Grecco H, Cordini G, Custidiano MDR, François JH, Berchem G, Borge M, Paggetti J, Moussay E, Gamberale R, Giordano M, Morande PE. Front Oncol. 11:598319 (2021). doi: 10.3389/fonc.2021.598319.
- Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia. Colado A, Elías EE, Sarapura Martínez VJ, Cordini G, Morande P, Bezares F, Giordano M, Gamberale R, Borge. Sci Rep. 11(1):12926 (2021). doi: 10.1038/s41598-021-92412-8.
- Expression and function of cathelicidin hCAP18/LL-37 in chronic lymphocytic leukemia. Podaza E, Palacios F, Croci DO, Risnik D, Yan XJ, Almejún MB, Colado A, Elías EE, Borge M, Morande PE, Bezares R, Fernández-Grecco H, Rabinovich GA, Gamberale R, Chiorazzi N, Giordano M. Haematologica. 105(9): e465-469 (2020). doi: 10.3324/haematol.2019.227975.
- The effect of ibrutinib on neutrophil and γδ T cell functions. Risnik D, Elías EE, Keitelman I, Colado A, Podaza E, Cordini G, Vergara Rubio M, Fernández Grecco H, Bezares RF, Borge M, Trevani A, Giordano M, Jancic C, Gamberale R. Leuk Lymphoma. 19:1-10 (2020). doi: 10.1080/10428194.2020.1753043.
- Second generation BTK inhibitors impair the anti-fungal response of macrophages and neutrophils. Colado A, Marín Franco JL, Elías EE, Amondarain M, Vergara Rubio M, Sarapura Martínez V, Cordini G, Fuentes F, Balboa L, Fernandez Grecco H, Pavlovsky M, Bezares F, Morande P, Giordano M, Gamberale R, Borge M. Am J Hematol. 95(7):E174-E178. (2020) doi: 10.1002/ajh.25816
- Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia. Risnik D, Colado A, Podaza E, Almejún MB, Elías EE, Bezares RF, Fernández-Grecco H, Seija N, Oppezzo P, Borge M, Gamberale R, Giordano M. Cancer Immunol Immunother. 69:813-824, (2020.) doi: 10.1007/s00262-020-02513-y.
- Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16high CD62Ldim immunosuppressive subset. Podaza E, Risnik D, Colado A, Elías E, Almejún MB, Fernandez Grecco H, Bezares RF, Borge M, Gamberale R, Giordano MInt J Cancer. 144:1128-34 (2019). doi: 10.1002/ijc.31762.
- Effect of the BTK inhibitor ibrutinib on macrophage- and γδ T cell-mediated response against Mycobacterium tuberculosis. Colado A, Genoula M, Cougoule C, Marín Franco JL, Almejún MB, Risnik D, Kviatcovsky D, Podaza E, Elías EE, Fuentes F, Maridonneau-Parini I, Bezares FR, Fernandez Grecco H, Cabrejo M, Jancic C, Sasiain MDC, Giordano M, Gamberale R, Balboa L, Borge M. Blood Cancer J. 8(11):100 (2018). doi: 10.1038/s41408-018-0136-x.
- Autologous T-cell activation fosters ABT-199 resistance in chronic lymphocytic leukemia: rationale for a combined therapy with SYK inhibitors and anti-CD20 monoclonal antibodies. Elías EE, Almejún MB, Colado A, Cordini G, Vergara-Rubio M, Podaza E, Risnik D, Cabrejo M, Fernández-Grecco H, Bezares RF, Custidiano MDR, Sánchez-Ávalos JC, Vicente Á, Garate GM, Borge M, Giordano M, Gamberale R. Haematologica. 103(10):e458-e461. (2018)doi: 10.3324/haematol.2018.188680.
2023
iwCLL Global Partnerships Biennial Meeting Grant para asistir al XX International Workshop on Chronic Lymphocytic Leukemia (XX iwCLL 2023) to Ana Colado, PhD.
2022
Arturo Falaschi short-term postdoctoral fellowship to Ana Colado, PhD. Directors: Mercedes Borge, PhD- Dimitar Efremov, PhD. International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
2020
American Society of Hematology Global Research Award 2020 to Mercedes Borge, PhD. https://www.hematology.org/awards/award-recipients/global-research-award-recipients