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Studying the Microenvironment And Related Targets in Non-Hodgkin's Lymphoma

Project description

Insight into the tumour microenvironment of lymphoid neoplasms

The tumour microenvironment (TME) is crucial in tumour evolution and therapy response, particularly for cancer immunotherapy. Funded by the Marie Skłodowska-Curie Actions programme, the SMART-NHL project focuses on chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL), two lymphoid neoplasms with relative similarities. The project aims to uncover the interplay between the TME and neoplastic cells in CLL and MCL. Researchers will employ single-cell analysis and 3D culture systems to study cellular interactions and identify molecular players that influence cancer progression and therapy resistance. Results could lead to new patient risk-stratification models and therapeutic targets.

Objective

The tumor microenvironment (TME) plays an essential role in tumor evolution and response to therapy. Understanding the complex network comprising tumor and immune cells is critical for the success of cancer immunotherapy. CLL and MCL are two non-Hodgkin’s lymphomas characterized by accumulating CD5+ small and mature B lymphocytes in peripheral blood, bone marrow, lymph nodes, and extranodal sites. Despite having distinct basic pathogenic mechanisms, they share the cell of origin and molecular alterations, clinical features, and epidemiological characteristics. However, the influence of the crosstalk between tumor cells and the TME on the disease progression and treatment resistance remains poorly understood, hindering the development of novel therapeutic possibilities.
This study aims to uncover the intricate interplay between the TME and neoplastic cells in CLL and MCL and exploit its therapeutic use. To achieve this, I will use single-cell RNA sequencing and spatial transcriptomics to analyze the composition of non-tumoral cells in tumor-involved tissues and at different time points of the disease. Next, I will use correlative analyses to identify the molecular and cellular interactions between the tumor cell (epi)genomic configuration and the TME, determining tumor evolution and response to therapy. Finally, I will validate the identified drivers of disease evolution and treatment resistance and examine their potential as a target for treatment using a 3D LN-derived culture system. The findings have the potential to provide a solid basis for establishing new models of patient risk stratification and identify potential therapeutic opportunities targeting interactions between tumor cells and their microenvironment.
Conducting this project at the Molecular Pathology of Lymphoid Neoplasms group of Prof. Dr. Elias Campo will provide me an opportunity to acquire essential technical and soft skills vital for advancing my career in research.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Net EU contribution
€ 181 152,96
Address
CARRER ROSSELLO 149
08036 Barcelona
Spain
Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost
No data