Pseudotemporal ordering of spatial lymphoid tissue microenvironment profiles trails Unclassified DLBCL at the periphery of the follicle

Abstract

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the Italian Foundation for Cancer Research (AIRC)

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All the datasets used in the study are publicly available at the following links:: https://onlinelibrary.wiley.com/doi/full/10.1002/eji.202149746 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32918 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10846 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117556

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