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The rise and fall of metastatic clones under immune attack

Project description

Immune system versus metastatic cancer cells

One of the hallmarks of cancer is metastasis: the ability of cancer cells to escape the primary tumour, migrate and colonise distant sites. Significant evidence over the years has highlighted the process, yet little is known about how these cells escape immune recognition. The EU-funded EVOMET project is focusing on colorectal cancer, which has a very low survival rate once metastatic. Researchers are working under the hypothesis that metastatic cancer cells escape immune surveillance through the suppression of neoantigens. Being able to quantify the relation between the immune system and tumour cells will pave the way for novel anti-cancer interventions. 

Objective

Colorectal cancer is the second most common cancer in Europe, and although screening has drastically increased survival, a fraction of patients still develops metastatic disease. These patients have a 5-year survival rate of 14% compared to 70% for those non-metastatic (SEER 18). For the majority of cases, the primary tumour is successfully resected, but disease relapse arises due to undetectable metastases. How metastatic clones arise within the primary tumor and adapt to their microenvironment acquiring the capacity of colonize new niches remain unknown. In this project, we aim to use evolutionary analysis combined with state of the art high-throughput technologies to analyse the relationship between the immune system and the progression to metastatic disease.
Recently, Zapata and colleagues analysed the relationship between natural selection and the immune system using more than 20 publicly available cancer datasets. The results demonstrated that the presence of neoantigens in the course of tumour development is constrained by the strength of immune activity (immunoediting). In metastasis, malignant clones must escape immune surveillance to colonise new environments. Therefore, we hypothesize that the presence of neoantigens under negative selection in primary tumours will inform us of the cancer cells' ability to disseminate, and ultimately, settle in distant niches. To test our hypothesis, we will develop a patient- specific method to quantify immunoediting across three different cohorts of primary-metastasis matched samples. Ultimately, the extent of immunoediting can be used to explain the underlying causes of metastatic progression allowing, in the future, the development of better treatment strategies.

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Coordinator

INSTITUTE OF CANCER RESEARCH: THE ROYAL CANCER HOSPITAL LBG
Net EU contribution
€ 224 933,76
Address
Old brompton road 123
SW7 3RP London
United Kingdom

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Region
London Inner London — West Kensington & Chelsea and Hammersmith & Fulham
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00