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

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

Research output: Contribution to journalArticlepeer-review

Abstract

We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZ mutational machinery 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 sub-classified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas.

Original languageEnglish
Pages (from-to)101562
JournaliScience
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 23 2020

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