Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral

ilustraciones, diagramas

Autores:: Ishikawa, Flávia Midori

Tipo de recurso:

Fecha de publicación:: 2024

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
network_name_str	Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
dc.title.translated.eng.fl_str_mv	Evaluation of the capacity of soluble or membrane-bound interleukin-15 to induce cytotoxic immune responses in a murine tumor model
title	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
spellingShingle	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral 610 - Medicina y salud::615 - Farmacología y terapéutica Interleucina-15/uso terapéutico Neoplasias/ tratamiento farmacológico Microambiente Tumoral Interleukin-15/therapeutic use Neoplasms/drug therapy Tumor Microenvironment Inmunoterapia Interleuquina-15 Citotoxicidad Modelos in vivo humanizados Cáncer Immunotherapy Interleukin-15 Cytotoxicity Humanized in vivo models Cancer
title_short	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
title_full	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
title_fullStr	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
title_full_unstemmed	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
title_sort	Evaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoral
dc.creator.fl_str_mv	Ishikawa, Flávia Midori
dc.contributor.advisor.spa.fl_str_mv	Muñoz Suárez, Alejandra Margarita Parra López, Carlos Alberto
dc.contributor.author.spa.fl_str_mv	Ishikawa, Flávia Midori
dc.contributor.projectleader.spa.fl_str_mv	Salguero López, Gustavo Andrés
dc.contributor.researchgroup.spa.fl_str_mv	Unidad de Terapias Avanzadas Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::615 - Farmacología y terapéutica
topic	610 - Medicina y salud::615 - Farmacología y terapéutica Interleucina-15/uso terapéutico Neoplasias/ tratamiento farmacológico Microambiente Tumoral Interleukin-15/therapeutic use Neoplasms/drug therapy Tumor Microenvironment Inmunoterapia Interleuquina-15 Citotoxicidad Modelos in vivo humanizados Cáncer Immunotherapy Interleukin-15 Cytotoxicity Humanized in vivo models Cancer
dc.subject.decs.spa.fl_str_mv	Interleucina-15/uso terapéutico Neoplasias/ tratamiento farmacológico Microambiente Tumoral
dc.subject.decs.eng.fl_str_mv	Interleukin-15/therapeutic use Neoplasms/drug therapy Tumor Microenvironment
dc.subject.proposal.spa.fl_str_mv	Inmunoterapia Interleuquina-15 Citotoxicidad Modelos in vivo humanizados Cáncer
dc.subject.proposal.eng.fl_str_mv	Immunotherapy Interleukin-15 Cytotoxicity Humanized in vivo models Cancer
description	ilustraciones, diagramas
publishDate	2024
dc.date.accessioned.none.fl_str_mv	2024-07-24T18:42:27Z
dc.date.available.none.fl_str_mv	2024-07-24T18:42:27Z
dc.date.issued.none.fl_str_mv	2024-06-26
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/86610
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/86610 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.indexed.spa.fl_str_mv	Bireme
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
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dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
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spelling	Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Muñoz Suárez, Alejandra Margarita038a9a8644782bf95ba8bd79650af287600Parra López, Carlos Alberto29924f3507fcedbca9501300464d5b61600Ishikawa, Flávia Midori8d3d0c6b247c3bcd64427257a5a84ac1600Salguero López, Gustavo AndrésUnidad de Terapias Avanzadas Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud2024-07-24T18:42:27Z2024-07-24T18:42:27Z2024-06-26https://repositorio.unal.edu.co/handle/unal/86610Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasLa IL-15 ha sido considerada por el National Cancer Institute como una de las inmunoterapias más promisoras para el tratamiento del cáncer, una molécula central en la activación de la inmunidad antiviral y antitumoral sin un aparente efecto dual, siendo excelente alternativa a la IL-2. La IL-15 interactúa con su receptor α formando un complejo IL-15/IL-15Rα en la membrana de células dendríticas, monocitos y macrófagos. Este complejo interactúa con los receptores IL-2Rβ/γ de las células T y NK en transpresentación, promoviendo la señalización necesaria para una potente activación y proliferación de estos tipos celulares. Sin embargo, los mecanismos y efectos de la activación celular de la IL-15/IL-15Rα no han sido completamente elucidados en el contexto humano in vivo, y se carecen de estudios en modelos preclínicos con mayor poder traslacional que puedan contribuir al entendimiento del rol de esta citoquina en el contexto clínico del cáncer. En este trabajo se investigó el potencial efecto in vivo de dos formas de complejo IL-15/IL-5Rα, uno anclado a la membrana y el otro en una forma soluble (IL-15mb vs IL-15s), en el crecimiento tumor de una línea de melanoma maligno humano. Para esto se utilizaron dos modelos murinos humanizados a partir de la cepa NRG, con la transferencia de leucocitos de sangre periférica (HuPBL) y con el trasplante de células progenitoras hematopoyéticas (HuHSC). En este estudio se demostró que la IL-15, en complejo con su receptor α, tiene un potente efecto antitumoral sobre las células inmunes, principalmente las células T y NK. El efecto antitumoral fue evidenciado a través de la reducción del crecimiento tumoral y mayor infiltración de dichas células en el tumor y en la sangre periférica. Este trabajo contribuye a la comprensión del efecto de la IL-15 en el microambiente tumoral, permitiendo identificar vías clave de esta molécula en la estimulación de la inmunidad antitumoral, lo que abre la puerta al desarrollo de posibles terapias novedosas para pacientes con cáncer. (Texto tomado de la fuente).IL-15 has been considered by the National Cancer Institute as one of the most promising immunotherapies for cancer treatment, serving as a central molecule in the activation of antiviral and antitumor immunity without apparent dual effects, making it an excellent alternative to IL-2. IL-15 is frequently bound to its receptor α, forming an IL-15/IL-15Rα complex on the membrane of dendritic cells, monocytes, and macrophages. This complex interacts with IL-2Rβ/γ receptors on T and NK cells in transpresentation, promoting the necessary signaling for potent activation and proliferation of these cells. The mechanisms of action have not been fully elucidated, and there is a lack of preclinical studies with higher translational power to contribute to understanding the role of this cytokine in the clinical context of cancer. This study investigated the potential in vivo effect of two IL-15/IL-5Rα agonists, one anchored to the membrane and the other in a soluble form (IL-15mb vs. IL-15s), on the tumor growth of a human malignant melanoma cell line. Two humanized murine models were utilized, derived from the NRG strain, with the transfer of peripheral blood leukocytes (HuPBL) and the transplantation of hematopoietic stem cells (HuHSC). Here, we demonstrated that IL-15, in complex with its α receptor, has a potent antitumor effect on immune cells, primarily T and NK cells. The antitumor effect was evidenced by the reduction in tumor growth and increased infiltration of these cells in the tumor and peripheral blood. This work contributes to the understanding of the IL-15 effect in the tumor microenvironment, identifying key pathways of this potent molecule in stimulation, leading to potential novel therapies for cancer patients.MaestríaMagíster en Ciencias - Biologíaxiii, 146 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - BiologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticaInterleucina-15/uso terapéuticoNeoplasias/ tratamiento farmacológicoMicroambiente TumoralInterleukin-15/therapeutic useNeoplasms/drug therapyTumor MicroenvironmentInmunoterapiaInterleuquina-15CitotoxicidadModelos in vivo humanizadosCáncerImmunotherapyInterleukin-15CytotoxicityHumanized in vivo modelsCancerEvaluación de la capacidad de la interleuquina-15 soluble o anclada a la membrana de inducir respuestas inmunes citotóxicas en un modelo murino tumoralEvaluation of the capacity of soluble or membrane-bound interleukin-15 to induce cytotoxic immune responses in a murine tumor modelTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeAkdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E., Klunker, S., Meyer, N., O’Mahony, L., Palomares, O., Rhyner, C., Quaked, N., Schaffartzik, A., Van De Veen, W., Zeller, S., Zimmermann, M., & Akdis, C. 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Cellular and Molecular Immunology, 19(2), 192–209. https://doi.org/10.1038/s41423-021-00786-6Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud - IDCBISEstudiantesInvestigadoresLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86610/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL965422.2024.pdf965422.2024.pdfTesis de Maestría en Ciencias - Biologíaapplication/pdf5435126https://repositorio.unal.edu.co/bitstream/unal/86610/2/965422.2024.pdfcd117ee0ad9f5fcd52fd49988f732359MD52THUMBNAIL965422.2024.pdf.jpg965422.2024.pdf.jpgGenerated Thumbnailimage/jpeg4385https://repositorio.unal.edu.co/bitstream/unal/86610/3/965422.2024.pdf.jpg212af6efaac377dc021d578be6392153MD53unal/86610oai:repositorio.unal.edu.co:unal/866102024-07-24 23:25:56.587Repositorio Institucional Universidad Nacional de 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