Lymphoma-derived IL-10 regulates the expression of L-type Ca²⁺ channels and associates with worse responses to conventional CD20 immunotherapy. (A) Comparison of survival curves (log-rank test) between pBIC and pBIC^Δ10 mice, either untreated or treated with anti- (α)CD20, after normalizing the time measurements to the initiation of treatment. (B) Genome Browser representation of STAT3-binding sites identified by ChIP-seq in human ABC-DLBCL cells (GSE106844³⁴). (C) Expression of Cacna1c by RNA-seq (log counts per million (logCPM) in FACS-sorted lymphoma cells (B220⁺GFP⁺) from pBIC and pBIC^Δ10 tumors (t test). (D) Expression of Cacna1c and Il-10 by RT-qPCR in pBIC lymphoma cells after 24-hour ex vivo treatment with 10 μg/mL of αIL-10R and concentrations slightly rounded over IC50 of ruxolitinib (100 μM) or pyrimethamine (200 μM; n = 3), as calculated in Figure 1E. Expression of each gene in untreated cells was used for normalization (ANOVA). (E) Normalized cell viability assays of pBIC/pBIC^Δ10 lymphoma cells (GFP⁺ 7AAD^–) studied by flow cytometry after 24 hours of ex vivo culture with increasing doses of αCD20 (t test), or (F) after 6 hours in the presence of 12.5 μg/mL of αCD20 with or without 20 mM of EDTA (n = 3; ANOVA). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ChIP-seq, chromatin immunoprecipitation-seq; h, hours; i.p., intraperitoneal; mRNA, messenger RNA; wk, week; OS, overall survival.