Tertiary Lymphoid Structures-associated macrophages

Tertiary Lymphoid Structures (TLS) are immune cell aggregates that are found within some tumours. Mature TLS are composed of a functional B cell germinal centre and a T cell zone, and myeloid cells including follicular dendritic cells and macrophages. Recently, TLS have been shown to be biomarkers of prolonged patient survival and enhanced response to immune checkpoint blockade, although the mechanisms remain to be elucidated. The phenotype and function of TLS-associated macrophages (TLS-TAMs) remain unknown. I will establish the phenotype of TLS-TAMs, in terms of surface markers, chemokine secreted, interaction with other cells and functionality. I will evaluate how TLS-TAMs affect patients' survival and response to immunotherapies. I will describe how TLS-TAMs are affected by macrophage-targeted cancer therapies. In a pan-cancer approach, this work will be conducted in various cancer types (colorectal, endometrial, ovarian and breast cancers) to evaluate whether TLS-TAMs vary between malignancies or have common features. I will use state-of-the-art spatially-resolved transcriptomics technologies. I will engage in computational method development to facilitate the analysis of this emerging data type. My project will help understand how TLS affect clinical outcome and allow to identify patients that could benefit from immunotherapy and macrophage depleting therapies to guide clinicians' therapeutic decision-making.