Authors
Wu, S., Lee, E., Fratzscher, A.-S., Lytle, A., Martin, S. D., Hsu, T., Telenius, A., Yin, Y., Fong, A., Rai, S., Fujisawa, M., Cheung, H., Aparicio, S., Huntsman, D. G., Aoki, T., Scott, D. W., Steidl, C., Roth, A.
Abstract
Histological examination of follicular lymphoma (FL) biopsies remains the cornerstone for diagnostic grading of FL. Single-cell sequencing approaches, while transcriptomically rich, require tissue dissociation and lose the native spatial context that underpins FL transformation to diffuse large B-cell lymphoma (DLBCL). To investigate the spatial interplay between malignant B-cells and the tumour microenvironment (TME) across disease states, we performed subcellular single-cell spatial transcriptomics and spatial proteomics on 12 paired pre/post-transformation samples and 10 non-transforming FL controls, integrated with matched single-cell whole genome sequencing (scWGS). Our analysis reveals that transformation is accompanied by a shift toward B-cell-predominant stromal and immunosuppressive cellular neighbourhoods, where the magnitude of expansion correlates with time to transformation. Prior to transformation, immunomodulatory Galectin-9 interactions move from the intra-follicular core to the extra-follicular space. Integration with scWGS demonstrates that high copy-number instability in malignant B-cells is associated with reduced supportive T-cell niches and intensified immunoregulatory crosstalk at the transformed state. Collectively, our multi-omic analysis characterizes TME remodeling during FL transformation, contributing to a refined disease evolution model.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 16 Aug 2026.
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