Fig. 5: TIS-associated myeloid plasticity underlies superior long-term outcome in DLBCL patients.

a Gene set enrichment analysis (GSEA) probing whole lymph-node (LN) lysate gene expression profiles (GEP) from newly diagnosed Eμ-myc lymphomas (GSE134751³⁹) with the perspective of cure (i.e. never-relapse [NR]; n = 20) vs. relapse (i.e. relapse-prone [RP]; n = 19) that were 4-hr in vivo cyclophosphamide (CTX)-challenged. Gene sets distinguishing murine myeloid cell types from B-cells and of associated TF targets are analyzed. Positive normalized enrichment scores (NES) signify enrichment in the NR + 4-hr CTX group. Enrichments with false discovery rate (FDR) < 0.05 are marked gray. b GSEA of the ‘macrophage (Mφ) vs. B-cell up’ gene set for lymphomas as in a, but as treatment-naïve at baseline. c Specimens as in b, but selected for CD19⁺ B-cells, (NR and RP; n = 16 each). d As in c, but probing a murine gene set that distinguishes dendritic cells (DC) from B-cells. e GSEA probing a human DC vs. B-cell signature in a data set of human diffuse large B-cell lymphoma (DLBCL) patients⁶⁸ that remained event-free (alive) or not (deceased). n = 513 vs. n = 238 patients, respectively. b–e Enrichment plots with their respective NES and FDR values. f Kaplan-Meier plot of tumor-free survival observed in Eμ-myc lymphoma-bearing mice after a single-dose of CTX, stratified by average expression levels of the top 100 ‘DC vs. B up’ genes in GEP of lymphoma LN 4-hr post in vivo CTX challenge as in (a). g Overall survival (OS) of rituximab, CTX, doxorubicin, vincristine and prednisone (R-CHOP)-treated DLBCL patients from two independent cohorts stratified by average expression levels of the human ‘DC vs. B up’ gene signature: the Duke cohort⁶⁸ (n = 751, left) and The International DLBCL Rituximab-CHOP Consortium Program (GSE31312; n = 470; right). f, g Survival curves reflect a median split and log-rank-based P values are shown. Source data are provided in the Source Data file.