Cytokine-linked remodeling of the immune microenvironment is a hallmark of transformation in follicular lymphoma [scRNA-seq]

Despite recent progress, understanding of the molecular and cellular underpinnings of transformation remains incomplete. Here, we dissect the interplay of tumor and microenvironment cell populations across transformation through a multimodal investigation of 85 FL and transformed FL samples, including single-cell and bulk RNA-sequencing alongside spatial transcriptomics and proteomics.

Upon transformation, GPNMB+ macrophages and fibroblasts with matrix-remodeling phenotypes increased while lymph-node organizing populations (e.g. follicular dendritic cells, CCL21-expressing fibroblastic reticular cells) were lost. Transformation was marked by altered spatial distribution of cytokines, impacting macrophage differentiation and T cell infiltration. This detection of secreted stromal and macrophage signals was further evident by non-invasive plasma proteomics.