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Interestingly, 80% of ST2/BN2 patients reached an early molecular response (EMR) and the 2 ST2/BN2 patients who did not achieve an EMR after 1 cycle of therapy are still in complete remission. Also in the validation cohort, patients with <2.5Log SB 10 sb hGE and/or assigned to cluster BN2 and ST2 presented an excellent outcome with a 40-month PFS and OS of 73.2% and 79.7%, compared to 39.2% and 44.8% for other patients, respectively (both I p i = 0.001) (Figure 1B). B Introduction: b The quantification of circulating tumor DNA (ctDNA) on the liquid biopsy at the time of diagnosis allows to stratify the outcome of diffuse large B-cell lymphoma (DLBCL) patients but its integration with molecular clustering has not been evaluated so far. [Extracted from the article]

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3 high patients displayed longer survival compared with NR1H3 low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)