Frontiers in Immunology (Aug 2023)

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

  • Claudio Tripodo,
  • Claudio Tripodo,
  • Giorgio Bertolazzi,
  • Giorgio Bertolazzi,
  • Valeria Cancila,
  • Gaia Morello,
  • Emilio Iannitto,
  • Emilio Iannitto

DOI
https://doi.org/10.3389/fimmu.2023.1207959
Journal volume & issue
Vol. 14

Abstract

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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.

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