Research Matthias Vanderkerken

Abstract

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western countries but remains incurable to date. CLL is characterized by an accumulation of clonal, mature CD5+ B-cells in the blood, bone marrow, and secondary lymph nodes. There is also increasing evidence that immune system dysfunction is a key feature of CLL. This leads to weakened antibody responses to pathogens and vaccines, an increase in autoimmune reactions, and a higher risk of secondary cancer. However, it remains unclear how this immune dysfunction arises and to what extent these abnormalities are already present in the early stages of the disease and in monoclonal B-cell lymphocytosis (MBL), an asymptomatic precursor stage. With this project, we aim to gain more insight into the cellular and molecular factors in the microenvironment that contribute to the progressive growth of malignant B-lymphocytes and the failure of normal immune responses in CLL. To achieve this, we will analyze the presence, immunophenotype, gene expression profiles, and function of various immune cells in samples from patients with CLL, MBL, and healthy controls. A better understanding of the immune environment in CLL could ultimately lead to the development of more effective, potentially curative treatments for CLL.

Researcher(s)

• Promoter: Vanderkerken Matthias

Research team(s)

• Laboratory for Experimental Hematology (LEH)

Project type(s)

• Research Project

Abstract

Chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) are among the most prevalent hematological malignancies, but remain incurable despite recent therapeutic advances. They are defined by a progressive expansion of mature clonal B cells. A striking feature of both diseases is their strong dependence on microenvironmental interactions that promote the survival and immune escape of malignant B cells. Remarkably, B-cell clones with typical features of CLL and FL are frequently found in asymptomatic individuals, but the factors that control progression of these premalignant clones to overt CLL or FL remain unknown. We propose a novel hypothesis whereby aberrant crosstalk between conventional dendritic cells (cDCs) and T cells underlies clonal progression of premalignant B cells, and constitutes a shared pathogenic mechanism in CLL and FL. In this project, we aim to provide a comprehensive overview of the cellular and molecular interactions in the immune environment at different stages of disease, using a single-cell and spatial transcriptomics approach. We will apply computational methods to identify alterations in T cells and/ or cDCs that drive disease progression, and validate key findings through ex vivo assays of T cell and cDC function and using innovative in vivo mouse models of CLL and FL. A better understanding of the immune alterations in these patients may benefit the development of novel immunotherapeutic approaches.

Researcher(s)

• Promoter: Vanderkerken Matthias
• Fellow: Vanderkerken Matthias

Research team(s)

• Laboratory for Experimental Hematology (LEH)

Project type(s)

• Research Project