The kinase inhibitors R406 and GS-9973 impair T cell functions and macrophage-mediated anti-tumor activity of rituximab in chronic lymphocytic leukemia patients
Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have s...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | , , , , , , , , , , , , |
| Formato: | Capítulo de libro |
| Lenguaje: | Inglés |
| Publicado: |
Springer Science and Business Media Deutschland GmbH
2017
|
| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
| Aporte de: | Registro referencial: Solicitar el recurso aquí |
| LEADER | 22548caa a22021257a 4500 | ||
|---|---|---|---|
| 001 | PAPER-15097 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518204545.0 | ||
| 008 | 190410s2017 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-85007173764 | |
| 024 | 7 | |2 cas |a CD40 ligand, 226713-27-5; chemokine receptor CCR7, 231617-75-7; chemokine receptor CXCR4, 188900-71-2; entospletinib, 1229208-44-9; fostamatinib, 901119-35-5; gamma interferon, 82115-62-6; protein kinase Syk, 138674-26-7; protein kinase ZAP 70, 148047-34-1; rituximab, 174722-31-7; 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine; Indazoles; N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine; Oxazines; Pyrazines; Pyridines; Receptors, Antigen, T-Cell; Rituximab; Syk Kinase; ZAP-70 Protein-Tyrosine Kinase | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a CIIMD | ||
| 100 | 1 | |a Colado, A. | |
| 245 | 1 | 4 | |a The kinase inhibitors R406 and GS-9973 impair T cell functions and macrophage-mediated anti-tumor activity of rituximab in chronic lymphocytic leukemia patients |
| 260 | |b Springer Science and Business Media Deutschland GmbH |c 2017 | ||
| 270 | 1 | 0 | |m Borge, M.; Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina (ANM), Pacheco de Melo 3081, Argentina; email: mercedesborge@hotmail.com |
| 506 | |2 openaire |e Política editorial | ||
| 504 | |a Soma, L.A., Craig, F.E., Swerdlow, S.H., The proliferation center microenvironment and prognostic markers in chronic lymphocytic leukemia/small lymphocytic lymphoma (2006) Hum Pathol, 37 (2), pp. 152-159. , COI: 1:CAS:528:DC%2BD28XlvVKqtw%3D%3D, PID: 16426914 | ||
| 504 | |a Rosati, S., Kluin, P.M., Chronic lymphocytic leukaemia: a review of the immuno-architecture (2005) Curr Top Microbiol Immunol, 294, pp. 91-107. , COI: 1:CAS:528:DC%2BD2MXhtlamsr%2FL, PID: 16323429 | ||
| 504 | |a Audrito, V., Vaisitti, T., Serra, S., Bologna, C., Brusa, D., Malavasi, F., Deaglio, S., Targeting the microenvironment in chronic lymphocytic leukemia offers novel therapeutic options (2013) Cancer Lett, 328 (1), pp. 27-35. , COI: 1:CAS:528:DC%2BC38XhsValsrjJ, PID: 22910767 | ||
| 504 | |a Bagnara, D., Kaufman, M.S., Calissano, C., Marsilio, S., Patten, P.E., Simone, R., Chum, P., Chiorazzi, N., A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease (2011) Blood, 117 (20), pp. 5463-5472. , COI: 1:CAS:528:DC%2BC3MXntFKqu7Y%3D, PID: 21385850 | ||
| 504 | |a Ghia, P., Strola, G., Granziero, L., Geuna, M., Guida, G., Sallusto, F., Ruffing, N., Caligaris-Cappio, F., Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22 (2002) Eur J Immunol, 32 (5), pp. 1403-1413. , COI: 1:CAS:528:DC%2BD38XjvFKjsLs%3D, PID: 11981828 | ||
| 504 | |a Granziero, L., Ghia, P., Circosta, P., Gottardi, D., Strola, G., Geuna, M., Montagna, L., Caligaris-Cappio, F., Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia (2001) Blood, 97 (9), pp. 2777-2783. , COI: 1:CAS:528:DC%2BD3MXjtlSiu7Y%3D, PID: 11313271 | ||
| 504 | |a Schmid, C., Isaacson, P.G., Proliferation centres in B-cell malignant lymphoma, lymphocytic (B-CLL): an immunophenotypic study (1994) Histopathology, 24 (5), pp. 445-451. , COI: 1:STN:280:DyaK2cznsV2itQ%3D%3D, PID: 8088716 | ||
| 504 | |a Patten, P.E., Buggins, A.G., Richards, J., Wotherspoon, A., Salisbury, J., Mufti, G.J., Hamblin, T.J., Devereux, S., CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment (2008) Blood, 111 (10), pp. 5173-5181. , COI: 1:CAS:528:DC%2BD1cXmtlahs7k%3D, PID: 18326821 | ||
| 504 | |a Crawford, D.H., Catovsky, D., In vitro activation of leukaemic B cells by interleukin-4 and antibodies to CD40 (1993) Immunology, 80 (1), pp. 40-44. , COI: 1:CAS:528:DyaK2cXmsFWq, PID: 7503945 | ||
| 504 | |a Buschle, M., Campana, D., Carding, S.R., Richard, C., Hoffbrand, A.V., Brenner, M.K., Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia (1993) J Exp Med, 177 (1), pp. 213-218. , COI: 1:CAS:528:DyaK3sXlslyqtw%3D%3D, PID: 7678114 | ||
| 504 | |a Kiaii, S., Kokhaei, P., Mozaffari, F., Rossmann, E., Pak, F., Moshfegh, A., Palma, M., Mellstedt, H., T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile (2013) Cancer Immunol Immunother, 62 (1), pp. 51-63. , COI: 1:CAS:528:DC%2BC3sXosl2qsg%3D%3D, PID: 22736254 | ||
| 504 | |a Braselmann, S., Taylor, V., Zhao, H., Wang, S., Sylvain, C., Baluom, M., Qu, K., Masuda, E.S., R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation (2006) J Pharmacol Exp Ther, 319 (3), pp. 998-1008. , COI: 1:CAS:528:DC%2BD28Xht1yltL7P, PID: 16946104 | ||
| 504 | |a Gobessi, S., Laurenti, L., Longo, P.G., Carsetti, L., Berno, V., Sica, S., Leone, G., Efremov, D.G., Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells (2009) Leukemia, 23 (4), pp. 686-697. , COI: 1:CAS:528:DC%2BD1MXks1Sitbk%3D, PID: 19092849 | ||
| 504 | |a Buchner, M., Baer, C., Prinz, G., Dierks, C., Burger, M., Zenz, T., Stilgenbauer, S., Zirlik, K., Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia (2010) Blood, 115 (22), pp. 4497-4506. , COI: 1:CAS:528:DC%2BC3cXnsFKntLo%3D, PID: 20335218 | ||
| 504 | |a Suljagic, M., Longo, P.G., Bennardo, S., Perlas, E., Leone, G., Laurenti, L., Efremov, D.G., The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Emu-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling (2010) Blood, 116 (23), pp. 4894-4905. , COI: 1:CAS:528:DC%2BC3cXhs1SlsrvP, PID: 20716772 | ||
| 504 | |a Friedberg, J.W., Sharman, J., Sweetenham, J., Johnston, P.B., Vose, J.M., Lacasce, A., Schaefer-Cutillo, J., Shipp, M.A., Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia (2010) Blood, 115 (13), pp. 2578-2585. , COI: 1:CAS:528:DC%2BC3cXksFOhs70%3D, PID: 19965662 | ||
| 504 | |a Currie, K.S., Kropf, J.E., Lee, T., Blomgren, P., Xu, J., Zhao, Z., Gallion, S., Mitchell, S.A., Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase (2014) J Med Chem, 57 (9), pp. 3856-3873. , COI: 1:CAS:528:DC%2BC2cXls1CrsL4%3D, PID: 24779514 | ||
| 504 | |a Sharman, J., Hawkins, M., Kolibaba, K., Boxer, M., Klein, L., Wu, M., Hu, J., Yasenchak, C., An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia (2015) Blood, 125 (15), pp. 2336-2343. , COI: 1:CAS:528:DC%2BC2MXmsl2ht7Y%3D, PID: 25696919 | ||
| 504 | |a Dubovsky, J.A., Beckwith, K.A., Natarajan, G., Woyach, J.A., Jaglowski, S., Zhong, Y., Hessler, J.D., Byrd, J.C., Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes (2013) Blood, 122 (15), pp. 2539-2549. , COI: 1:CAS:528:DC%2BC3sXhs1CgsrfK, PID: 23886836 | ||
| 504 | |a Borge, M., Belen Almejun, M., Podaza, E., Colado, A., Fernandez Grecco, H., Cabrejo, M., Bezares, R.F., Gamberale, R., Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages (2015) Haematologica, 100 (4), pp. e140-e142. , PID: 25616578 | ||
| 504 | |a Da Roit, F., Engelberts, P.J., Taylor, R.P., Breij, E.C., Gritti, G., Rambaldi, A., Introna, M., Golay, J., Ibrutinib interferes with the cell-mediated anti-tumour activities of therapeutic CD20 antibodies: implications for combination therapy (2014) Haematologica, 100 (1), pp. 77-86. , PID: 25344523 | ||
| 504 | |a Montalvao, F., Garcia, Z., Celli, S., Breart, B., Deguine, J., Van Rooijen, N., Bousso, P., The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging (2013) J Clin Investig, 123 (12), pp. 5098-5103. , COI: 1:CAS:528:DC%2BC3sXhvFSqur7O, PID: 24177426 | ||
| 504 | |a Uchida, J., Hamaguchi, Y., Oliver, J.A., Ravetch, J.V., Poe, J.C., Haas, K.M., Tedder, T.F., The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy (2004) J Exp Med, 199 (12), pp. 1659-1669. , COI: 1:CAS:528:DC%2BD2cXltFKlurs%3D, PID: 15210744 | ||
| 504 | |a Leonhardt, F., Zirlik, K., Buchner, M., Prinz, G., Hechinger, A.K., Gerlach, U.V., Fisch, P., Zeiser, R., Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels (2012) Leukemia, 26 (7), pp. 1617-1629. , COI: 1:CAS:528:DC%2BC38XhtVelsrjL, PID: 22301676 | ||
| 504 | |a Platt, A.M., Benson, R.A., McQueenie, R., Butcher, J.P., Braddock, M., Brewer, J.M., McInnes, I.B., Garside, P., The active metabolite of spleen tyrosine kinase inhibitor fostamatinib abrogates the CD4(+) T cell-priming capacity of dendritic cells (2015) Rheumatology, 54 (1), pp. 169-177. , PID: 25065010 | ||
| 504 | |a Chattopadhyay, P.K., Yu, J., Roederer, M., Live-cell assay to detect antigen-specific CD4+ T-cell responses by CD154 expression (2006) Nat Protoc, 1 (1), pp. 1-6. , COI: 1:CAS:528:DC%2BD28XhtFOitbzO, PID: 17406204 | ||
| 504 | |a Borge, M., Nannini, P.R., Galletti, J.G., Morande, P.E., Avalos, J.S., Bezares, R.F., Giordano, M., Gamberale, R., CXCL12-induced chemotaxis is impaired in T cells from patients with ZAP-70-negative chronic lymphocytic leukemia (2010) Haematologica, 95 (5), pp. 768-775. , COI: 1:CAS:528:DC%2BC3cXht1yrsbzM, PID: 20145264 | ||
| 504 | |a Geginat, J., Sallusto, F., Lanzavecchia, A., Cytokine-driven proliferation and differentiation of human naive, central memory and effector memory CD4+ T cells (2003) Pathol Biol, 51 (2), pp. 64-66. , COI: 1:CAS:528:DC%2BD3sXktl2gsrs%3D, PID: 12801802 | ||
| 504 | |a Geginat, J., Lanzavecchia, A., Sallusto, F., Proliferation and differentiation potential of human CD8 + memory T-cell subsets in response to antigen or homeostatic cytokines (2003) Blood, 101 (11), pp. 4260-4266. , COI: 1:CAS:528:DC%2BD3sXktFKht7o%3D, PID: 12576317 | ||
| 504 | |a Palacios, E.H., Weiss, A., Distinct roles for Syk and ZAP-70 during early thymocyte development (2007) J Exp Med, 204 (7), pp. 1703-1715. , COI: 1:CAS:528:DC%2BD2sXnslyls7s%3D, PID: 17606633 | ||
| 504 | |a Feldman, A.L., Sun, D.X., Law, M.E., Novak, A.J., Attygalle, A.D., Thorland, E.C., Fink, S.R., Dogan, A., Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas (2008) Leukemia, 22 (6), pp. 1139-1143. , COI: 1:CAS:528:DC%2BD1cXntVCjtb8%3D, PID: 18401419 | ||
| 504 | |a Noraz, N., Schwarz, K., Steinberg, M., Dardalhon, V., Rebouissou, C., Hipskind, R., Friedrich, W., Taylor, N., Alternative antigen receptor (TCR) signaling in T cells derived from ZAP-70-deficient patients expressing high levels of Syk (2000) J Biol Chem, 275 (21), pp. 15832-15838. , COI: 1:CAS:528:DC%2BD3cXjvFais7o%3D, PID: 10748099 | ||
| 504 | |a Krishnan, S., Juang, Y.T., Chowdhury, B., Magilavy, A., Fisher, C.U., Nguyen, H., Nambiar, M.P., Tsokos, G.C., Differential expression and molecular associations of Syk in systemic lupus erythematosus T cells (2008) J Immunol, 181 (11), pp. 8145-8152. , COI: 1:CAS:528:DC%2BD1cXhtl2gsLrI, PID: 19018007 | ||
| 504 | |a Hauck, F., Blumenthal, B., Fuchs, S., Lenoir, C., Martin, E., Speckmann, C., Vraetz, T., Latour, S., SYK expression endows human ZAP70-deficient CD8 T cells with residual TCR signaling (2015) Clin Immunol, 161 (2), pp. 103-109. , COI: 1:CAS:528:DC%2BC2MXhsFertLrM, PID: 26187144 | ||
| 504 | |a Buchner, M., Fuchs, S., Prinz, G., Pfeifer, D., Bartholome, K., Burger, M., Chevalier, N., Zirlik, K., Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia (2009) Cancer Res, 69 (13), pp. 5424-5432. , COI: 1:CAS:528:DC%2BD1MXnvFajsro%3D, PID: 19549911 | ||
| 504 | |a Hallek, M., Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment (2015) Am J Hematol, 90 (5), pp. 446-460. , COI: 1:CAS:528:DC%2BC2MXntFSnsrc%3D, PID: 25908509 | ||
| 504 | |a Mocsai, A., Ruland, J., Tybulewicz, V.L., The SYK tyrosine kinase: a crucial player in diverse biological functions (2010) Nat Rev Immunol, 10 (6), pp. 387-402. , COI: 1:CAS:528:DC%2BC3cXlvFOkurk%3D, PID: 20467426 | ||
| 504 | |a Bojarczuk, K., Siernicka, M., Dwojak, M., Bobrowicz, M., Pyrzynska, B., Gaj, P., Karp, M., Winiarska, M., B-cell receptor pathway inhibitors affect CD20 levels and impair antitumor activity of anti-CD20 monoclonal antibodies (2014) Leukemia, 28 (5), pp. 1163-1167. , COI: 1:CAS:528:DC%2BC2cXhsl2nu7o%3D, PID: 24492323 | ||
| 504 | |a Jain, N., O’Brien, S., Targeted therapies for CLL: practical issues with the changing treatment paradigm (2015) Blood Rev, 30 (3), pp. 233-244. , PID: 26776345 | ||
| 504 | |a Kohrt, H.E., Sagiv-Barfi, I., Rafiq, S., Herman, S.E., Butchar, J.P., Cheney, C., Zhang, X., Byrd, J.C., Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity (2014) Blood, 123 (12), pp. 1957-1960. , COI: 1:CAS:528:DC%2BC2cXls1OjtbY%3D, PID: 24652965 | ||
| 504 | |a Herman, S.E., Gordon, A.L., Wagner, A.J., Heerema, N.A., Zhao, W., Flynn, J.M., Jones, J., Johnson, A.J., Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals (2010) Blood, 116 (12), pp. 2078-2088. , COI: 1:CAS:528:DC%2BC3cXht1KisbbF, PID: 20522708 | ||
| 504 | |a Ravandi, F., O’Brien, S., Immune defects in patients with chronic lymphocytic leukemia (2006) Cancer Immunol Immunother, 55 (2), pp. 197-209. , PID: 16025268 | ||
| 504 | |a Weinblatt, M.E., Kavanaugh, A., Genovese, M.C., Musser, T.K., Grossbard, E.B., Magilavy, D.B., An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis (2010) N Engl J Med, 363 (14), pp. 1303-1312. , COI: 1:CAS:528:DC%2BC3cXht1WqsLfI, PID: 20879879 | ||
| 504 | |a Barr, P.M., Saylors, G.B., Spurgeon, S.E., Cheson, B.D., Greenwald, D.R., O’Brien, S.M., Liem, A.K., Friedberg, J.W., Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL (2016) Blood, 127 (20), pp. 2411-2415. , COI: 1:CAS:528:DC%2BC28Xhs1ent7jP, PID: 26968534 | ||
| 504 | |a Okkenhaug, K., Burger, J.A., PI3 K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL) (2016) Curr Top Microbiol Immunol, 393, pp. 123-142. , PID: 26350103 | ||
| 504 | |a Kiefer, F., Brumell, J., Al-Alawi, N., Latour, S., Cheng, A., Veillette, A., Grinstein, S., Pawson, T., The Syk protein tyrosine kinase is essential for Fc gamma receptor signaling in macrophages and neutrophils (1998) Mol Cell Biol, 18 (7), pp. 4209-4220. , COI: 1:CAS:528:DyaK1cXkt1Wjtro%3D, PID: 9632805 | ||
| 520 | 3 | |a Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients. This effect could not be ascribed to Syk-inhibition given that we show that T cells from CLL patients do not express Syk protein. Interestingly, ζ-chain-associated protein kinase (ZAP)-70 phosphorylation was diminished by both inhibitors upon TCR stimulation on T cells. In addition, we found that both agents reduced macrophage-mediated phagocytosis of rituximab-coated CLL cells. Overall, these results suggest that in CLL patients treated with R406 or GS-9973 T cell functions, as well as macrophage-mediated anti-tumor activity of rituximab, might be impaired. The potential consequences for CLL-treated patients are discussed. © 2016, Springer-Verlag Berlin Heidelberg. |l eng | |
| 536 | |a Detalles de la financiación: Novartis | ||
| 536 | |a Detalles de la financiación: Ministério da Ciência, Tecnologia e Inovação, MCTI | ||
| 536 | |a Detalles de la financiación: AbbVie | ||
| 536 | |a Detalles de la financiación: PICT 1074/2013, PICT 1310/2012 | ||
| 536 | |a Detalles de la financiación: Bristol-Myers Squibb | ||
| 536 | |a Detalles de la financiación: This work was supported by grants from Fondo para la Investigaci?n Cient?fica y Tecnol?gica (PICT 1074/2013 and PICT 1310/2012), Ministry of Science, Technology and Innovation, Argentina. We are indebted to Beatriz Loria, Mar?a Tejeda and Federico Fuentes for their technical assistance. Romina Gamberale had received compensation as speaker for Janssen and Bristol-Myers Squibb, as speaker and consultant for Roche, and as a member of the advisory board of AbbVie. Raimundo Fernando Bezares had received compensation as speaker from Novartis, Varifarma and Roche. All | ||
| 593 | |a Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina (ANM), Pacheco de Melo 3081, Buenos Aires, 1425, Argentina | ||
| 593 | |a Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina | ||
| 593 | |a Servicio de Patología Molecular, Instituto de Investigaciones Hematológicas-ANM, Buenos Aires, Argentina | ||
| 593 | |a Laboratorio de Genética de Neoplasias Linfoides, IMEX-CONICET-ANM, Buenos Aires, Argentina | ||
| 593 | |a Departamento de Hematología, Sanatorio Julio Méndez, Buenos Aires, Argentina | ||
| 593 | |a Sección de Hematología, Hospital General de Agudos Dr. Teodoro Álvarez, Buenos Aires, Argentina | ||
| 593 | |a Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina | ||
| 690 | 1 | 0 | |a BCR-ASSOCIATED KINASE INHIBITORS |
| 690 | 1 | 0 | |a CHRONIC LYMPHOCYTIC LEUKEMIA |
| 690 | 1 | 0 | |a GS-9973 |
| 690 | 1 | 0 | |a R406 |
| 690 | 1 | 0 | |a SYK INHIBITORS |
| 690 | 1 | 0 | |a CD40 LIGAND |
| 690 | 1 | 0 | |a CHEMOKINE RECEPTOR CCR7 |
| 690 | 1 | 0 | |a CHEMOKINE RECEPTOR CXCR4 |
| 690 | 1 | 0 | |a ENTOSPLETINIB |
| 690 | 1 | 0 | |a FOSTAMATINIB |
| 690 | 1 | 0 | |a GAMMA INTERFERON |
| 690 | 1 | 0 | |a INTERLEUKIN 10 |
| 690 | 1 | 0 | |a INTERLEUKIN 4 |
| 690 | 1 | 0 | |a PROTEIN KINASE SYK |
| 690 | 1 | 0 | |a PROTEIN KINASE ZAP 70 |
| 690 | 1 | 0 | |a RITUXIMAB |
| 690 | 1 | 0 | |a 6-(1H-INDAZOL-6-YL)-N-(4-MORPHOLINOPHENYL)IMIDAZO(1,2-A)PYRAZIN-8-AMINE |
| 690 | 1 | 0 | |a INDAZOLE DERIVATIVE |
| 690 | 1 | 0 | |a LYMPHOCYTE ANTIGEN RECEPTOR |
| 690 | 1 | 0 | |a N4-(2,2-DIMETHYL-3-OXO-4H-PYRID(1,4)OXAZIN-6-YL)-5-FLUORO-N2-(3,4,5-TRIMETHOXYPHENYL)-2,4-PYRIMIDINEDIAMINE |
| 690 | 1 | 0 | |a OXAZINE DERIVATIVE |
| 690 | 1 | 0 | |a PROTEIN KINASE SYK |
| 690 | 1 | 0 | |a PROTEIN KINASE ZAP 70 |
| 690 | 1 | 0 | |a PYRAZINE DERIVATIVE |
| 690 | 1 | 0 | |a PYRIDINE DERIVATIVE |
| 690 | 1 | 0 | |a RITUXIMAB |
| 690 | 1 | 0 | |a ANTINEOPLASTIC ACTIVITY |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CANCER PATIENT |
| 690 | 1 | 0 | |a CD4+ T LYMPHOCYTE |
| 690 | 1 | 0 | |a CELL MIGRATION |
| 690 | 1 | 0 | |a CHRONIC LYMPHATIC LEUKEMIA |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a CYTOKINE RELEASE |
| 690 | 1 | 0 | |a HUMAN |
| 690 | 1 | 0 | |a HUMAN CELL |
| 690 | 1 | 0 | |a LYMPHOCYTE ACTIVATION |
| 690 | 1 | 0 | |a LYMPHOCYTE FUNCTION |
| 690 | 1 | 0 | |a LYMPHOCYTE PROLIFERATION |
| 690 | 1 | 0 | |a MACROPHAGE |
| 690 | 1 | 0 | |a PHAGOCYTOSIS |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a PROTEIN PHOSPHORYLATION |
| 690 | 1 | 0 | |a UPREGULATION |
| 690 | 1 | 0 | |a AGED |
| 690 | 1 | 0 | |a ANTAGONISTS AND INHIBITORS |
| 690 | 1 | 0 | |a CELL CULTURE |
| 690 | 1 | 0 | |a CELL PROLIFERATION |
| 690 | 1 | 0 | |a DRUG EFFECTS |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a IMMUNOLOGY |
| 690 | 1 | 0 | |a LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL |
| 690 | 1 | 0 | |a LYMPHOCYTE ACTIVATION |
| 690 | 1 | 0 | |a MALE |
| 690 | 1 | 0 | |a METABOLISM |
| 690 | 1 | 0 | |a MIDDLE AGED |
| 690 | 1 | 0 | |a PHOSPHORYLATION |
| 690 | 1 | 0 | |a T LYMPHOCYTE |
| 690 | 1 | 0 | |a VERY ELDERLY |
| 690 | 1 | 0 | |a AGED |
| 690 | 1 | 0 | |a AGED, 80 AND OVER |
| 690 | 1 | 0 | |a CELL PROLIFERATION |
| 690 | 1 | 0 | |a CELLS, CULTURED |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a HUMANS |
| 690 | 1 | 0 | |a INDAZOLES |
| 690 | 1 | 0 | |a LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL |
| 690 | 1 | 0 | |a LYMPHOCYTE ACTIVATION |
| 690 | 1 | 0 | |a MACROPHAGES |
| 690 | 1 | 0 | |a MALE |
| 690 | 1 | 0 | |a MIDDLE AGED |
| 690 | 1 | 0 | |a OXAZINES |
| 690 | 1 | 0 | |a PHAGOCYTOSIS |
| 690 | 1 | 0 | |a PHOSPHORYLATION |
| 690 | 1 | 0 | |a PYRAZINES |
| 690 | 1 | 0 | |a PYRIDINES |
| 690 | 1 | 0 | |a RECEPTORS, ANTIGEN, T-CELL |
| 690 | 1 | 0 | |a RITUXIMAB |
| 690 | 1 | 0 | |a SYK KINASE |
| 690 | 1 | 0 | |a T-LYMPHOCYTES |
| 690 | 1 | 0 | |a ZAP-70 PROTEIN-TYROSINE KINASE |
| 700 | 1 | |a Almejún, M.B. | |
| 700 | 1 | |a Podaza, E. | |
| 700 | 1 | |a Risnik, D. | |
| 700 | 1 | |a Stanganelli, C. | |
| 700 | 1 | |a Elías, E.E. | |
| 700 | 1 | |a Dos Santos, P. | |
| 700 | 1 | |a Slavutsky, I. | |
| 700 | 1 | |a Fernández Grecco, H. | |
| 700 | 1 | |a Cabrejo, M. | |
| 700 | 1 | |a Bezares, R.F. | |
| 700 | 1 | |a Giordano, M. | |
| 700 | 1 | |a Gamberale, R. | |
| 700 | 1 | |a Borge, M. | |
| 773 | 0 | |d Springer Science and Business Media Deutschland GmbH, 2017 |g v. 66 |h pp. 461-473 |k n. 4 |p Cancer Immunol. Immunother. |x 03407004 |t Cancer Immunology, Immunotherapy | |
| 856 | 4 | 1 | |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85007173764&doi=10.1007%2fs00262-016-1946-y&partnerID=40&md5=383022ba5e891a2ba74d6b5b4db33deb |y Registro en Scopus |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00262-016-1946-y |y DOI |
| 856 | 4 | 0 | |u https://hdl.handle.net/20.500.12110/paper_03407004_v66_n4_p461_Colado |y Handle |
| 856 | 4 | 0 | |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03407004_v66_n4_p461_Colado |y Registro en la Biblioteca Digital |
| 961 | |a paper_03407004_v66_n4_p461_Colado |b paper |c PE | ||
| 962 | |a info:eu-repo/semantics/article |a info:ar-repo/semantics/artículo |b info:eu-repo/semantics/publishedVersion | ||
| 999 | |c 76050 | ||