Caracterización de la Interacción entre Célula Madre Tumoral y Microambiente Inmune en el Cáncer de Pulmón no Microcítico

Non-small cell lung cancer (NSCLC) is one of the solid tumors with the highest mortality in the world. The acquisition of treatment¿s resistances, together with the lack of treatment¿s effectiveness on Cancer Stem Cells (CSCs) and evading immune mechanism produced by the tumor are one of the main ca...

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Detalles Bibliográficos
Autor: Torres Martínez, Susana
Tipo de recurso: tesis de maestría
Fecha de publicación:2017
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:español
OAI Identifier:oai:riunet.upv.es:10251/86114
Acceso en línea:https://riunet.upv.es/handle/10251/86114
Access Level:acceso abierto
Palabra clave:Cancer stem cell
Lung cancer
Immunity
Microenvironment
NSCPC
Célula madre tumoral
CPNM
CSC
Microambiente
Inmunidad
Cáncer de pulmón
MICROBIOLOGIA
Máster Universitario en Biotecnología Biomédica-Màster Universitari en Biotecnologia Biomèdica
Descripción
Sumario:Non-small cell lung cancer (NSCLC) is one of the solid tumors with the highest mortality in the world. The acquisition of treatment¿s resistances, together with the lack of treatment¿s effectiveness on Cancer Stem Cells (CSCs) and evading immune mechanism produced by the tumor are one of the main causes of the high mortality. CSCs in NSCLC are targets poorly recognized by immune surveillance system, making an important mechanism of tumor immune evasion which favors an immunosuppressive microenvironment which is crucial during tumorigenesis. What is more, immune cells in the tumor microenvironment are able to modulate the tumor cells, making acquire stem-like characteristics, favouring further progression, recurrence, metastasis and resistance to treatment. Consequently, due to the fact that interactions between CSCs and immune cells are involved in the down-regulation of the immune response allowing tumor escape from immune surveillance, a better understanding on how CSCs interacts with their immune microenvironment in NSCLC will result in an improved characterization of patient¿s immune contexture (through the use of biomarkers). The aim of this work is the characterization of the interactions between CSCs and its immune microenvironment. The study is performed on NSCLC cultures (cell lines and primary tumor cell cultures) and used to: (i) analyse the CSC¿s production of soluble factors ( cytokines, growth factors) with immunosuppresive or immunoregulator capacity by multiplexed assays (Luminex), (ii) determine the influence of soluble factors produced by lung tumorspheres on different populations of immune cells, and (iii) identify mechanism involved in the modulation of immune cells function by CSCs. In conclusion this study has a translation approach through the validation of the findings made during the exploratory phase of this work, on the search for biomarkers in cohorts of CPNM patients and immune design strategies adapt to each patient. Moreover, the results of this study will result in the development of new targeting molecules modulating interactions between CSCs and the microenvironment immune tumoral, in order to remove the population of CSCs