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Dietary neuro-immunomodulation of metastasis

Personalized therapy, immunotherapy and cancer

Senior Researcher : Nabil Djouder

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Research Centre or Institution : Centro Nacional de Investigaciones Oncológicas (CNIO). Madrid

Abstract

Despite significant progress in cancer research and treatment, cancer remains a leading cause of death and a significant burden on public health, primarily because of its ability to metastasize and the limited effectiveness of available treatments, including immune checkpoint inhibitors (ICIs). Ongoing efforts are dedicated to developing new treatment strategies aimed at improving therapeutic interventions against metastases and reducing mortality rates.

Diet plays a significant role in cancer, triggering diverse physiological responses that impact tumor incidence, development, and treatment outcomes. Strong evidence from preclinical models and early clinical studies suggests that low carbohydrate diets (LCDs) can aid in cancer prevention and treatment. However, their effects on metastasis remain unknown, and the underlying mechanisms are unclear.

This proposal seeks to investigate the influence of LCDs and other harmful diets on metastasis using a multi- and inter-disciplinary approach. This involves integrating mouse models with state-of-the-art technologies in genomics, neuroscience, immunology, and advanced imaging techniques, along with the use of human and clinical data and tissues to determine how LCD could impact metastasis.

The complex relationships within the LCD-brain axis will be studied to decode nutritional and metabolic effects that can finely modulate the nervous-immune system and control metastasis. Dietary effects on cholinergic immunosurveillance to relieve the highly complex immunosuppressive microenvironment in metastasis will be thoroughly analysed to unveil the consequences of dietary interventions on the effectiveness of ICIs.

This proposal aims to implement a clear path towards the clinical application of dietary interventions and provide broad foundations for future holistic and personalized therapeutic explorations against metastasis.

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