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

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...

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Detalles Bibliográficos
Autores principales: Tripodo, Claudio, Zanardi, Federica, Iannelli, Fabio, Mazzara, Saveria, Vegliante, Mariella, Morello, Gaia, Di Napoli, Arianna, Mangogna, Alessandro, Facchetti, Fabio, Sangaletti, Sabina, Chiodoni, Claudia, VanShoiack, Alison, Jeyasekharan, Anand D., Casola, Stefano, Colombo, Mario P., Ponzoni, Maurilio, Pileri, Stefano A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522121/
https://www.ncbi.nlm.nih.gov/pubmed/33083730
http://dx.doi.org/10.1016/j.isci.2020.101562
Descripción
Sumario: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.