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

ongoing

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.