Scoring IL-10–associated transcriptional hallmarks stratifies patients with DLBCL with distinct responses to standard-of-care R-CHOP. (A) Heat map of ssGSEA values (z scores) of 3 genetic signatures (TREG, ANGIO, and CAL) in patients with DLBCL from Schmitz et al² (n = 243). Samples are ranked by the SILX score calculated for each sample (shown at the bottom). Predicted correspondences with preclinical mouse models are depicted. (B) Survival analysis of this cohort stratified by SILX values. (C) Multivariate cox proportional hazard analysis including ECOG, COO, LymphGen (genetic subtypes), and SILX group. (D) Sankey plots showing the distribution of each SILX group in defined COO and LymphGen subtypes (left). Survival curves for the SILX-stratified patients within the more aggressive (ABC and MCD-N1) or less aggressive (GCB and ST2-EZB-A53-BN2) subtypes (right). Red represents SILX^High; dark blue represents SILX^{Low + Med}; medium blue, SILX^Low; light blue, SILX^Med. (E) Percentage of SILX^High, SILX^Med, or SILX^Low samples that belong to each microenvironment group defined by Kotlov et al⁷⁵ (top; green) or to each lymphoma ecotype defined by Steen et al⁷⁶ (middle; red); and average of normalized ssGSEA values for several IL-10–associated microenvironment hallmarks (bottom; blue). (F) Survival analysis in the validation cohort (n = 1390). (G) Multivariate Cox proportional hazard analysis including COO and SILX annotations in the validation cohort (left). Survival curves of SILX-stratified patients from the validation cohort within ABC and GCB subtypes (right). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. ANGIO, angiogenesis; CAL, calcium activity; DEP, depleted; ECOG, Eastern Cooperative Oncology Group performance status; GCL, germinal center-like; HR, hazard ratio; INF, inflammatory; MACRO, macrophages; MES, mesenchymal; OS, overall survival; TIL, tumor infiltrating lymphocytes; TREG, T regulatory cells; UNC, unclassified.