A novel lymphoma-associated macrophage interaction signature (LAMIS) provides robust risk prognostication in diffuse large B-cell lymphoma clinical trial cohorts of the DSHNHL

Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy. Transcriptomics dataset of 330 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with Diffuse large B-cell lymphoma (DLBCL). Gene Expression profiles of 145 target genes were created using the NanoString nCounter technology (NanoString Technologies, Seattle, WA). The name of the study cohort was included to help distinguish the samples. ***Submitters state that the corresponding clinical data is not provided due to privacy protections, refering to the following data sharing agreement and the Leipzig Health Atlas: Pseudonymised data will be available upon request up to 5 years after publication of this Article to researchers who provide a data sharing agreement that describes a methodically sound proposal and the data necessary for the purpose of the approved proposal. Proposals should be directed to [e-mail]. Data will be shared once all relevant parties approve and sign the data sharing agreement. Selected data will be also available on the Leipzig Health Atlas website. For the Leipzig Health Atlas website see www.health-atlas.de.