A Spatially Resolved Dark- versus Light-Zone Microenvironment Signature Subdivides Germinal Center-Related Aggressive B Cell Lymphomas

Claudio Tripodo, Saveria Mazzara, Federica Zanardi, Mariella Vegliante, Stefano A. Pileri, Fabio Iannelli, Arianna Di Napoli, Alison Vanshoiack, Sabina Sangaletti, Claudio Tripodo, Claudia Chiodoni, Stefano Casola, Maurilio Ponzoni, Fabio Facchetti, Mario P. Colombo, Anand D. Jeyasekharan, Gaia Morello

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

We applied digital spatial profiling for 87 immune and stromal genes to lymphnode germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest toobtain a differential signature of these two distinct microenvironments. Thespatially resolved 53-genes signature, comprising key genes of the DZ mutationalmachinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit (DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were subclassified into two clusters. The subgroups differed in the distribution of DH casesand survival, with most DH displaying a distinct DZ-like profile. The clusteringanalysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first timeachieving DZ/LZ discrimination based on stromal/immune features. The reportoffers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas.
Original languageEnglish
Pages (from-to)101562-
Number of pages18
JournaliScience
Volume23
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • General

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