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[Background]: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment., [Methods]: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared., [Results]: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination., [Conclusion]: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.

Este TFG tiene como objetivo evaluar el efecto de diferentes combinaciones y patrones de cultivos simultáneos asociados entre melón y judía de careta, con incorporación de los residuos vegetales como abono verde, la reducción de la profundidad del arado y la reducción en el uso de insumos externos en el rendimiento de las cosechas, biodiversidad y calidad de suelo durante un ciclo de cultivo. Para ello se van a comparar cultivos individuales de melón con sus asociaciones con judía en filas alternas 1:1, filas alternas 2:1, o mezclado en la misma fila. Al final del ciclo se determinará la producción, la relación equivalente del terreno y la calidad de la cosecha. Además, se tomarán muestras de suelo para verificar si la asociación de cultivos contribuye al incremento de nutrientes. En paralelo, durante el ciclo de cultivo se realizará un monitoreo de de la incidencia de plagas y biodiversidad de entomofauna.

En el último trimestre del año 2007 comenzó la crisis financiera internacional afectando a la economía española, entre otras. Este hecho provocó una drástica destrucción de empleo en nuestro país, aumentado el número de beneficiarios de pensiones y prestaciones públicas y, a su vez, afectando a las fuentes de financiación de dichas prestaciones. De esta forma, en la actualidad se da un desequilibrio en la balanza de la Tesorería General de la Seguridad Social