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Contenido archivado el 2024-06-18

Influence of hypoxia in the tumor microenvironment on the adaptive immune response and cancer immunotherapy

Objetivo

The tumor microenvironment determines many of the hallmarks of cancer. Stromal components and malignant cells dialogue and mutually change their functional responses. Tumor infiltrating lymphocytes (TILs) are a prominent feature of solid tumors, whose presence has correlation with a better survival in cancer-patients. However TILs are severely restrained in their ability to tackle tumors as a result of immunosuppressive mechanisms. This proposal is based on the hypothesis that low levels of oxygen availability in solid tumors induce profound changes on the adaptative immune response mediated by HIF-1α and HIF-2α transcription factors. Research objectives include: 1) To study TILs behaviour under hypoxia 2) To explore the molecular mechanisms underlying the observed changes, and importantly, 3) To evaluate the impact of these changes for different immunotherapeutic strategies (monoclonal antibodies, adoptive transfers, and drugs targeting the hypoxia pathway).
The state-of-the-art technical approaches to address these objectives include cutting-edge two-photon in vivo imaging to study the immune response inside hypoxic tumors, and unique-in-the-world transgenic mice to unravel the HIF-1α and HIF-2α pathway importance in T cells.
This project will enable a more rational design of anti-tumor immunotherapies and could help to explain disease recurrence and identify potential targets for therapeutic interventions.

Ámbito científico (EuroSciVoc)

Programa(s)

Tema(s)

Convocatoria de propuestas

FP7-PEOPLE-2012-IEF
Consulte otros proyectos de esta convocatoria

Régimen de financiación

MC-IEF - Intra-European Fellowships (IEF)

Coordinador

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Aportación de la UE
€ 221 606,40
Dirección
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
Reino Unido
Región
East of England East Anglia Cambridgeshire CC
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos