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Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous malignancy. Advances in transcriptomic and genetic profiling have significantly enhanced our understanding of the disease's intrinsic pathogenesis, uncovering numerous potential therapeutic targets. However, the impact of tumor-infiltrating Regulatory T cells (Tregs) on the prognosis of DLBCL remains controversial. Here, we developed a Treg-associated gene signature by integrating single-cell and bulk transcriptome data to predict the prognosis of DLBCL patients receiving standard immunochemotherapy. In total, 227 Tregs feature genes were identified, six of which were selected for constructing a prognostic signature. DLBCL patients possessing high-risk scores had significantly poorer survival outcomes than those who possess low-risk scores in NCICCR and validation cohorts. Mutations in PIM1, MYD88, DTX1, CARD11, CD79B, ETV6, BCL6, and CDKN2A were predominantly observed in the high-risk group, whereas alterations in TNFRSF14 and DNMT3A were more frequently detected in the low-risk group. Immune infiltration analysis revealed that the high-risk group exhibited an immunosuppressive microenvironment, whereas the low-risk group showed a higher abundance of non-cellular components in the tumor microenvironment (TME). Finally, the Treg features TNFRSF25 and SELL can effectively predict long-term responses to Axicabtagene Ciloleucel (Axi-cel) treatment. In summary, our study developed a prognostic signature consisting of six Treg feature genes by integrating single-cell and bulk transcriptomics to predict clinical outcomes in DLBCL patients. The risk signature was significantly associated with immunological characteristics., (© 2025 John Wiley & Sons Ltd.)

Background: Diffuse large B-cell lymphoma (DLBCL) is predominant subtype of non-Hodgkin lymphoma and can be effectively treated. Nevertheless, a subset of patients experiences refractory or relapsed disease, highlighting the need for new therapeutic strategies., Methods: Depmap database based on CRISPR/Cas9 knock out analysis was employed to identify the essential gene SH3GL1, which encodes endophilin A2, as crucial for the proliferation and survival of DLBCL cells. Immunohistochemistry (IHC) staining was performed on the 126 paraffin-embedded clinical DLBCL samples to investigate the association between SH3GL1 expression levels and the prognosis. To investigate the specific mechanism modulated by SH3GL1 in the progression of DLBCL, an integrative approach was employed. This approach combined high-throughput sequencing technologies, such as Deep-DIA and LC-MS, with functional validation techniques, including CRISPR/Cas9 gene editing, xenograft models, and molecular pathway analyses., Results: Our study found that high expression levels of SH3GL1 correlate with poor prognosis in a cohort of 126 newly diagnosed DLBCL patients, underscoring its significance in disease progression. Mechanistically, we found that SH3GL1 deficiency triggers ferritin heavy chain 1 (FTH1)-mediated ferroptosis, specifically ferritinophagy-induced ferroptosis, in DLBCL cells. Additionally, high expression of SH3GL1 suppresses doxorubicin-induced ferroptosis. Cancer cells' resistance to conventional therapies is associated with increased sensitivity to ferroptosis., Conclusions: These findings emphasise SH3GL1 as a promising prognostic biomarker and a potential therapeutic target in DLBCL, offering new avenues for treatment strategies aimed at overcoming drug resistance and improving patients' outcomes., Key Points: Elevated SH3GL1 expression in DLBCL patients was associated with a negative prognosis. SH3GL1 plays a crucial role in promoting DLBCL cell survival through the regulation of FTH1-mediated ferroptosis and doxorubicin resistance., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin's lymphoma (NHL). Ferroptosis is a novel form of cell death involved in multiple tumor development. However, the relationship between ferroptosis-related genes and DLBCL has not been extensively studied. The GSE95290 dataset was downloaded from the Gene Expression Omnibus (GEO) database and merged with genes associated with ferroptosis to screen differentially expressed genes (DEGs). Hub genes were identified by constructing a protein-protein interaction (PPI) network. The messenger RNA (mRNA) expressions of hub genes were subsequently detected in vitro using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The impact of voltage dependent anion channel 1 (VDAC1) on the proliferation, apoptosis, and ferroptosis of DLBCL was evaluated using Cell Counting Kit-8, flow cytometry, and relevant ferroptosis assays, respectively. Six highly expressed hub genes were identified, all of which could be used as diagnostic biomarkers for DLBCL. In vitro studies revealed that suppressing VDAC1 expression inhibited DLBCL cell proliferation and promoted apoptosis. Furthermore, knockdown of VDAC1 promoted ferroptosis in DLBCL cells and xenograft tumor models, resulting in elevated levels of malondialdehyde (MDA) and iron and increased protein levels of Acyl-CoA synthetase long-chain family 4 (ACSL4) and cyclooxygenase-2 (COX2). Conversely, glutathione (GSH) and superoxide dismutase (SOD) levels were reduced, accompanied by decreased protein levels of glutathione peroxidase 4 (GPX4) and ferritin heavy chain1 (FTH1). VDAC1 knockdown induces ferroptosis in DLBCL, which provides new insights into the pathogenic mechanisms of DLBCL., (© 2025 John Wiley & Sons Ltd.)

Introduction: Diffuse large B-cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B-cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high-risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2., Methods: Tissue samples from 111 DLBCL patients were sequenced with a 90-gene lymphoma panel, followed by integrative analyses combining sequencing data, immunohistochemistry, fluorescent in situ hybridization, and clinical data., Results: We identified a high-risk subgroup in DLBCL defined by: dual immunohistochemical MYC and BCL2 expression (DEL), concurrent MYC and BCL2 translocations (DHL-BCL2), mutations in MYC, CXCR4, or both, and/or BCL2 amplification. The high-risk subgroup constituted 41% of the cohort and included DHL-BCL2, DEL, a GCB subgroup likely representing the recently described GCB subgroups, and a subset of non-GCB patients. In multivariate analysis, high-risk features provided independent predictive value from age and IPI. The 5-year overall survival was 36% in high-risk patients, compared to 76% in non-high-risk patients., Conclusion: We identified a distinct high-risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL-BCL2 and DEL, and irrespective of cell-of-origin, thereby expanding the poor-prognosis group., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Accurate prevalence estimates of diffuse large B-cell lymphoma (DLBCL) are important for numerous purposes including orphan drug designation. A key criterion for orphan drug designation is a disease prevalence of less than 5/10,000 persons. The objective is to apply and compare different methods of prevalence assessment., Methods: In the present nationwide Danish cohort study, the prevalence of DLBCL was assessed using different methodologies, including register-based and formula-based approaches., Results: The prevalence calculations were based on 9,492 patients diagnosed with DLBCL since year 2000. Incidence increased and survival improved in the period, resulting in higher prevalence of DLBCL. In year 2023, the 2-,3-,5-,10-, and 20-year prevalences were 1.53, 2.19, 3.45, 6.08, and 8.80 per 10,000 adults using the register-based approach. The formula-based approach was generally accurate when using restricted mean survival. However, when using median survival, the total prevalence was estimated at 8.1 per 10,000 adults. Furthermore, when extrapolating the median survival from the 5-year survival under constant hazard assumption as done in some orphan drug designation reports, the prevalence was estimated at 6.6 per 10,000 adults., Conclusions: In conclusion, the estimated DLBCL prevalences are sensitive to the applied method. DLBCL would disqualify from orphan drug designation in some of the mentioned scenarios., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite advances in treatment, approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) who achieve complete remission (CR) after first-line therapy will experience a relapse. However, there is no consensus on the optimal follow-up strategies for detecting relapse after achieving CR. This population-based study, based on the Danish Lymphoma Registry (LYFO), identified a total of 1634 patients diagnosed with DLBCL between 2010 and 2017, including 105 patients who achieved CR following first-line R-CHOP-like therapy and subsequently relapsed. The median follow-up time was 6 years (range 3-8 years). Most cases of relapse were symptomatic (83%), with B symptoms and peripheral lymphadenopathy being the most common. Asymptomatic relapses were identified through physical examination (1%), blood tests (3%), or imaging findings (13%). The proportion of relapses identified outside routine visits was 70%. Only 5% of scheduled routine visits led to a relapse diagnosis, whereas 74% of unscheduled visits initiated by the patient outside routine follow-up resulted in relapse detection. Our findings highlight that systematic, scheduled monitoring of patients in remission after first-line treatment contributes only modestly to the early detection of disease recurrence. Future studies should explore alternative methods of relapse surveillance rather than relying solely on pre-scheduled clinical follow-up., (© 2025 Wiley Periodicals LLC.)

Background: Long noncoding RNAs (lncRNAs) have emerged as key regulators of cancer; in addition, they have been identified as novel therapeutic targets and biomarkers for several cancers, including diffuse large B-cell lymphoma (DLBCL)., Methods: A total of 75 DLBCL patients and 30 control subjects with active lymph nodes were enrolled into our study. The baseline expression levels of lncRNAs HOTAIR, MALAT1, and PANDA in paraffin-embedded blocks of lymph nodes from DLBCL patients and controls were evaluated using reverse transcription quantitative real-time PCR (RTqPCR) technique., Results: The expression levels of HOTAIR and MALAT1 were increased while PANDA expression level was decreased in DLBCL patients when compared to controls and in R-CHOP-resistant patients when compared to responder ones. Also, HOTAIR, MALAT1, and PANDA baseline expression levels were significantly correlated with the different clinical parameters in this study. As diagnostic and prognostic tools, the results obtained from the ROC curve revealed that the PANDA baseline expression level was the best one as the diagnostic biomarker could differentiate DLBCL disease and the prognostic biomarker predicts R-CHOP resistance., Conclusion: In conclusion, the integrated approach reveals that lncRNAs HOTAIR and MALAT1 were upregulated, while lncRNA PANDA was downregulated in DLBCL patients compared with controls, and the three lncRNAs closely associated with clinical prognosis. This study warrants future studies in clinical trials for the treatment of R-CHOP-resistant DLBCL patients., (© 2025 John Wiley & Sons Ltd.)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, characterized by its aggressive nature and heterogeneity. This study analyzes recent trends in DLBCL including trends in hospitalization, inpatient mortality, and costs., Methods: Using the Nationwide Inpatient Sample (NIS) database from 2016 until 2020, a retrospective cohort study was performed to identify DLBCL hospitalization, discharges, and investigate outcomes. Trends were adjusted for age, sex, race, insurance type, mean household income, and hospital characteristics. Multivariable logistic regression has been used to analyze the data., Results: A total of 103,588,729 records were analyzed, identifying 47,425 cases with a diagnosis of DLBCL. From 2016 to 2020, hospitalizations have increased from 14,980 to 16,565. The mean age at diagnosis was 65 (P < 0.001). Males were slightly more affected than females (57.3 vs 42.6), with an increasing trend in males from 53.7% to 62.3% (P = 0.03). The highest prevalence was observed in the White population, followed by Hispanics and African Americans. Notably, the prevalence among Hispanics increased from 10 to 12%, while there is a decreasing trend in other demographics (P = 0.05). Medicare was the most common insurance, with increasing trends, followed by Medicaid and private insurance (P = 0.6). Inpatient mortality increased from 6.1 to 7.1 (2016 to 2018) and decreased to 6.1% (2018 to 2020) (P < 0.001). The mean length of the stay remained stable at 11.8 days. However, hospital charges increased from $176,131 to $212,324. Comorbidities such as obesity, hypertension, other associated lymphomas, peripheral vascular diseases, and diabetes showed an increasing trend (P < 0.05). Discharges to home and skilled nursing facility (SNF) decreased, while there was an increase in discharges to home with home health (HH) care and short-term care (P < 0.001)., Conclusion: Risk factors for DLBCL include white male sex, with the mean age of 65 years. The incidence among the Hispanic population has been increasing over the years. There are disparities in incidence and survival among different ethnic/demographic groups that need to be addressed by identifying targeted interventions and equitable healthcare access., Competing Interests: Declarations. Conflict of interests: The authors declare that they have no conflict of interests. Ethics approval and consent to participate: Not applicable. Informed consent: Not applicable. Institutional review board approval: Not needed as the data have been collected from public databases., (© 2025. The Author(s).)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous subtype of non-Hodgkin lymphoma, with two-thirds of patients relapsing or resisting existing therapies, highlighting the urgent need for effective treatments. Toosendanin (TSN), a triterpenoid from Meliae Cortex, exhibits significant anti-cancer activity by modulating cell survival and proliferation. This study investigates the anti-lymphoma effects and underlying mechanisms of TSN, proposing it as a potential therapeutic agent to address the challenges of DLBCL. Network pharmacology, molecular docking, and transcriptome sequencing were employed to predict TSN's anti-DLBCL potential. Findings were validated through in vitro and in vivo experiments, including cell viability assays, flow cytometry, quantitative PCR, Western blotting, reverse experiments with small-molecule inhibitors or genetic editing, and a cell-derived xenograft (CDX) model. Bioinformatics analyses revealed TSN's strong binding affinity to PI3Kα/β and Polo-like kinase 1 (PLK1). Experiments showed that TSN downregulated the PI3K/Akt signaling pathway and reduced PLK1 mRNA and protein levels, inducing apoptosis, cell cycle arrest, and cell death in DLBCL cells. RNA sequencing and metabolic assays indicated TSN upregulated cholesterol biosynthesis in DLBCL cells. Co-treatment with a statin enhanced TSN's anti-DLBCL effects while mitigating hepatic and pulmonary toxicity. This study identifies TSN as a dual inhibitor of PI3K and PLK1 with significant therapeutic potential for DLBCL. It also proposes a lipid-modulating strategy to enhance TSN's cytotoxicity while reducing adverse effects, offering a promising approach to improve DLBCL treatment outcomes., (© 2025 John Wiley & Sons Ltd.)

Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but there are limited real-world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high-grade B cell lymphoma treated with R-GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy (n = 100), those utilizing R-GemOx as a bridge to ASCT or CAR T (n = 83), and those aged 70 and older (n = 71). Overall response rates (ORRs) for all patients treated with R-GemOx were 45% with a complete response (CR) rate of 29%. The median event-free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R-GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R-GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R-GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R-GemOx in the rapidly evolving landscape of R/R DLBCL therapies., (© 2025 Wiley Periodicals LLC.)

Purpose: The objective of this investigation is to explore the capability of baseline 18 F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI)., Methods: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index)., Results: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05)., Conclusions: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Fourth Hospital of Hebei Medical University (No.2022KY288). Consent to participate: The requirement of informed consent was waived., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Despite the association between aberrant TGFBI expression and tumors development found in various cancer types, the role of TGFBI in diffuse large B-cell lymphoma (DLBCL) progression is not clear. This study attempted to reveal how TGFBI impacts malignant progression and cisplatin sensitivity in DLBCL. Bioinformatics and qRT-PCR were used to analyze expression of TGFBI. To investigate the effect of TGFBI on malignant progression and cisplatin sensitivity in DLBCL cells, cell viability and IC50 values were assessed by CCK-8. Cell proliferation ability was detected by colony formation assay. Cell apoptosis rate was detected by flow cytometry. The degree of DNA damage in cells from different treatment groups was detected by comet assay. Protein expression of TGF-β pathway-related proteins like TGF-β1, Smad2, and p-Smad2 was detected by western blot. Bioinformatics and molecular experiments results revealed substantial upregulation of TGFBI in DCBCL. Cell experiment results indicated that high TGFBI expression expedited DCBCL progression and reduced cisplatin sensitivity. Further rescue experiments revealed that SB525334, a TGF-β pathway inhibitor, could weaken the acceleration of DCBCL progression and restore reduced cisplatin sensitivity both induced by high TGFBI expression. TGFBI could promote malignant progression and inhibit the cisplatin sensitivity of DLBCL cells by regulating the TGF-β pathway. In brief, TGFBI has the potential to be a target in DLBCL treatment., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were conducted strictly in accordance with the requirements of the The Lab of Animal Experimental Ethical Inspection of Dr.CanBiotechnology(Zhejiang) Co.,Ltd Animal Ethics Committee. Reference Number: DRK202409202. Consent to participate: Patient consent were not required in accordance with local or national guidelines. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Epcoritamab, a bispecific T-cell engager (BiTE) antibody targeting CD3 and CD20, has shown significant efficacy in treating refractory diffuse large B-cell lymphoma (DLBCL). However, its use can lead to severe side effects, such as tumor flare. Here, we report the case of an 84-year-old male with relapsed DLBCL who developed fatal unilateral pleural effusion following Epcoritamab treatment. Initially, the patient showed a favorable response, but later developed significant pleural effusion with elevated interleukin-6 (IL-6) levels, indicating a severe inflammatory response. This suggests that Epcoritamab directly affected the pleural lesions and caused a local cytokine release syndrome (L-CRS). Despite aggressive management, including Tocilizumab and Dexamethasone, the patient's condition worsened, leading to his death. This case underscores the importance of regular lab tests and imaging follow-ups to monitor and manage severe inflammatory reactions based on tumor location. Comprehensive monitoring protocols are needed to mitigate risks associated with novel immunotherapies. To our knowledge, this is the first reported case of fatal unilateral pleural effusion in a patient with relapsed DLBCL following Epcoritamab treatment., Competing Interests: Declarations. Patient consent statement: Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a major therapeutic challenge due to its resistance to standard treatments. Engineered T-cells, especially Chimeric Antigen Receptor (CAR) T-cells, have shown promise in overcoming drug resistance. This study investigates the effectiveness of WEE1-engineered T-cells in targeting and eliminating refractory DLBCL in vitro. CAR T-cells were created by transducing a 5th-generation CAR construct designed to recognize WEE1, a surface antigen commonly found on refractory DLBCL cells. The cytotoxic effect of engineered T-cells was tested against Rituximab-resistant DLBCL cells (RR-NU-DUL-1). Apoptosis and cell cycle were evaluated using flow cytometry. Quantitative Real-time PCR (RT-PCR) was used to measure the expression of WEE1, BCL2, and CDK2. The results showed a significant increase in target cell lysis, apoptosis, and necrosis, a significant reduction in the percentage of cells in the G2M phase of the cell cycle, as well as a decrease in gene expression level, indicating strong anti-tumor activity. These findings suggest that CAR T-cell therapy holds great promise for treating refractory DLBCL, offering a potential path for clinical application. This in vitro evaluation highlights the potential of WEE1-engineered T-cells as a targeted treatment strategy for refractory DLBCL, emphasizing their clinical applicability and ability to overcome resistance mechanisms in this aggressive lymphoma subtype., Competing Interests: Declarations. Financial and non-financial interests: The authors have no relevant financial or non-financial interests to disclose. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adult, characterized by uncontrolled cell proliferation and strong aggressiveness. Previous studies have found that cyclin-dependent kinase 1(CDK1) are related to tumor growth and metastasis. However, the role of CDK1 in DLBCL is exclusive. This study investigated the clinical implications and expression of CDK1 in DLBCL., Methods: Gene expression data for healthy subjects were sourced from the Genotype-Tissue Expression repository. Clinical details and survival statistics of patients with DLBCL were obtained from the Gene Expression Omnibus archive (GSE10846). Patients were categorized based on CDK1 expression levels, and differences in clinical outcomes between the groups were examined. Univariate and multivariate Cox regression analyses were used to ascertain whether CDK1 expression independently predicted DLBCL prognosis. The protein expression of CDK1 was gauged by immunohistochemistry. Additionally, we investigated the effect of CDK1 inhibition on DLBCL cell growth and death using the Cell Counting Kit-8 and flow cytometry., Results: In the control group, CDK1 expression was predominantly observed in the hematopoietic and reproductive systems. CDK1 levels in patients with DLBCL were notably elevated compared with those in controls. Significant differences were noted in the lactate dehydrogenase ratio and overall survival based on CDK1 expression. Statistical analyses confirmed that CDK1 was an independent predictor of DLBCL outcomes. Elevated CDK1 protein levels were observed in a significant number of DLBCL samples, in contrast to normal lymph node samples from individuals without lymphoma. The inhibitor Ro-3306 curtails DLBCL cell growth and enhances cell death in vitro., Conclusions: Elevated CDK1 levels are correlated with poor prognosis in patients with DLBCL., Competing Interests: Declarations. Ethics approval and consent to participate: All experiments on humans and/or the use of human tissue samples were performed in accordance with relevant guidelines and regulations. Informed consent from all of the participants in the study was obtained. The research conducted on human participants underwent a thorough evaluation and received approval from the Institutional Review Board (IRB) of the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University(KY-2023-181-01). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The International Prognostic Index (IPI) is the most frequently used tool for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of all ages. This study validated and compared six models developed for patients above 60 with International Prognostic Indices (IPI, R-IPI, NCCN-IPI). Moreover, we created a clinical nomogram with an online tool for individualized predictions. A total of 2,835 patients aged over 60 with newly diagnosed DLBCL treated with potentially curative immunochemotherapy were identified in the Danish Lymphoma Registry. A nomogram was developed by combining NCCN-IPI variables (excluding extranodal localization), albumin, and platelet levels in 1,970 patients and verified the results in the remaining 956 patients. Compared to other models, the elderly IPI (E-IPI) and age-adjusted IPI (aaIPI) showed better accuracy and discriminatory ability. However, the models failed to identify a high-risk group with a 3-year overall survival rate below 40%. Our nomogram-based model demonstrated superior discriminatory ability and provided more precise individual predictions than all other models based on a risk stratification system. Most clinical prognostic models fail to accurately predict patient outcomes in patients over 60 years old. Therefore, nomogram-based models should be considered in this population to prevent information loss due to variable dichotomization., Competing Interests: Declarations. Competing interests: JJ has received travel support from AstraZeneca and Roche. PB has served on advisory boards for Roche, Abbvie, and SERB. TSL has served on advisory boards/consultancy for Roche, Novartis, Gilead, and BMS. TSL received a research Grant from Genentech and travel support from Roche. Other authors have no relevant financial or non-financial interests to disclose. Ethical approval and consent to participate: This study was performed in accordance with the principles of the Declaration of Helsinki. The Advisory Board for Clinical Quality Development Program (RKKP) (project number 21/27006) has granted approval for conducting this registry-based study, ensuring total anonymity of patients. Further details can be found in the Declaration on passing personal data covered by § 10, a subsection of the Data Protection Act, 1 and 2’, https://www.retsinformation.dk/eli/lta/2019/1509 . Therefore, informed consent from patients was not obtained., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China. This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola-R-CHP and 469 R-CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 12.8 months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.3% vs. 84.1%, p = 0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG ≥ 2, extranodal involvement ≥ 2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p = 0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola-R-CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted., (© 2024 John Wiley & Sons Ltd.)

Although CD20xCD3 bispecific antibodies (BsAbs) have demonstrated transformational activity in diffuse large B-cell lymphoma (DLBCL), some patients fail to respond and others relapse. To begin to explore possible limitations, we compared the in vitro activity of four CD20xCD3 biosimilar BsAbs against four DLBCL cell lines with CD20 expression ranging over a 100-fold. All four biosimilar BsAbs demonstrated superior in vitro activity to rituximab, with biosimilar glofitamab consistently being the most potent. Moreover, biosimilar glofitamab and odronextamab retained significant activity in the presence of low-level CD20 expression. Finally, one DLBCL cell line exhibited intrinsic resistance to all four CD20xCD3 BsAbs despite inducing marked T-cell and NK-cell activation., (© 2025 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The PIM family of serine/threonine kinases (PIM1, PIM2, and PIM3) are involved in the development of cancer and represent promising therapeutic targets. We investigated the therapeutic potential of targeting PIM kinases in diffuse large B-cell lymphoma (DLBCL), particularly the activated B-cell-like (ABC) subtype, using the pan-PIM inhibitor AZD1208. We demonstrated that PIM1 and PIM2 are more highly expressed in ABC- cells than in germinal center B-cell-like (GCB) -DLBCL cells, and that ABC-DLBCL cell lines are more sensitive to PIM inhibition with AZD1208. Transcriptome analysis of ABC-DLBCL cell lines treated with AZD1208 revealed a downregulation of genes involved in NF-κB signaling, a crucial pathway for ABC-DLBCL. We also explored synergistic drug combinations using a high-throughput screen, which identified BCL2 and glutaminase inhibitors as effective partners for AZD1208, particularly in aggressive ABC-DLBCL and double-hit cell lines. The combination of AZD1208 with the clinically available BCL2 inhibitor venetoclax was synergistic in most DLBCL cell lines, and this combination induced apoptosis and reduced levels of AKT and MCL1 proteins. In conclusion, our findings suggested that AZD1208, especially when combined with BCL2 inhibitors like venetoclax, holds promise as a treatment strategy for aggressive lymphomas. These combinations may enable lower doses of PIM inhibitors, leading to increased tolerability and improved anti-tumor activity in clinical settings. The study also highlighted the potential for targeting PIM kinases in combination with other therapies to overcome drug resistance in DLBCL., (© 2025 John Wiley & Sons Ltd.)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid tumor, and accounts for approximately 30-40% of non-Hodgkin lymphomas. Although the prognosis has significantly improved with the advent of rituximab combination chemotherapy in the early 2000s, recurrence still occurs in about 40% of cases. Even though chemotherapy with increased dose-intensity is used in recurrent cases, the prognosis of such patients remains poor. Thus, the development of personalized medicine, including molecular-targeted drugs, is required to improve the prognosis of DLBCL patients, and further understanding of the molecular pathogenesis of DLBCL is essential for this purpose. With recent advances in genetic analysis technology, unknown genetic abnormalities and gene expression patterns have been discovered, and based on these discoveries, progress is being made in elucidating and subdividing molecular pathologies. This article summarizes recent findings regarding molecular pathogenesis in DLBCL using transcriptome and genomics technologies, and outlines the path to personalized medicine., Competing Interests: Declarations. Conflict of interest: D.E.: research funding from Nippon-shinyaku, Chugai and Eisai; honoraria from Eisai, Kyowa Kirin, Chugai, SymBio, Bristol Myers Squibb and Nippon-shinyaku., (© 2024. Japanese Society of Hematology.)

Competing Interests: Declarations. Competing interests: The authors declare no competing interests.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.1 (OR = 1.26, P = 1.17 × 10 -8 ), rs11066015 on 12q24.12 (OR = 1.24, P = 6.57 × 10 -9 ) and rs6032662 on 20q13.12 (OR = 1.24, P = 5.22 × 10 -12 ). Fine mapping analysis revealed that the extensive association within the MHC region was driven by two novel HLA alleles, HLA-A*02 and HLA-DQB1*03. Functional annotation, eQTL and colocalization analyses of the susceptibility loci implicated NFKBIE/TCTE1, ALDH2/BRAP and CD40 as candidate disease genes. The pleiotropic effect analysis of the DLBCL loci revealed shared genetic susceptibility between DLBCL and several autoimmune diseases. Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most common histological types of B-cell lymphoma, but have significantly different pathological and biological characteristics. In recent years, understanding of the genetic abnormalities and microenvironmental structures of these lymphomas has progressed, and various molecular targeted drugs and immunotherapies have been introduced into clinical practice. Therefore, accurate understanding of etiology and its clinical relevance is required for the appropriate management of these lymphomas., Competing Interests: Declarations. Conflict of interest: D.E.: research funding from Nippon-shinyaku, Chugai and Eisai; honoraria from Eisai, Kyowa Kirin, Chugai, SymBio, Bristol Myers Squibb and Nippon-shinyaku., (© 2025. The Author(s), under exclusive licence to Japanese Society of Hematology.)

The aim of this study is to explore the role of the IL-10/STAT3 pathway in the upregulation of natural killer group 2, member D (NKG2D) ligands (MICA and ULBP2) induced by Bruton's tyrosine kinase (BTK) inhibitors in non-germinal center B-cell-like diffuse large B-cell lymphoma cells. The expression levels of NKG2D ligands and the IL-10/STAT3 pathway in SUDHL4, U2932, and OCI-LY3 cells were analyzed using western blotting. After stimulation of the B-cell receptor signaling pathway with IgM antibodies, the expression levels of NKG2D ligands, as well as IL-10 and phosphorylated STAT3 (p-STAT3) were significantly reduced. In contrast, treatment with ibrutinib produced effects opposite to those induced by IgM antibodies. Additionally, treatment of U2932 and OCI-LY3 cells with the STAT3 inhibitor (STAT3-IN-1) led to an increase in NKG2D ligand expression and a decrease in IL-10 levels. When IL-10 neutralizing antibodies were introduced, p-STAT3 levels decreased, and NKG2D ligand expression increased. Similar outcomes were observed when the BTK inhibitors ACP-196 and BGB-3111 were administered. Our findings suggest that the IL-10/STAT3 pathway plays a key role in the upregulation of NKG2D ligands induced by BTK inhibitors in U2932 and OCI-LY3 cells., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Dysregulation of amino acid metabolism is recognized to have a substantial influence on tumorigenesis and the modulation of tumor microenvironment. However, the role of amino acid metabolism-related genes in diffuse large B-cell lymphoma (DLBCL) remains undefined. Therefore, we aimed to explore the influence of amino acid metabolism-related genes in DLBCL using bioinformatics approaches. Consensus clustering demonstrated that the reprogramming of amino acid metabolism has prognostic value in DLBCL. Subsequently, we developed a risk model using LASSO-Cox regression analysis to accurately predict DLBCL prognosis and identified kynureninase (KYNU) as a potentially valuable biomarker. Analysis of immune infiltration was conducted to examine the correlation between risk scores and immune profiles. Furthermore, RT-qPCR showed that the KYNU mRNA levels were upregulated in OCI-LY1, OCI-LY3, and OCI-LY10 DLBCL cells compared with normal CD19+B lymphocytes. Cell proliferation assays and flow cytometry analysis showed that inhibition of KYNU expression reduced cell proliferation and induced apoptosis of DLBCL cells. Overall, we demonstrated the significant impact of amino acid metabolism on DLBCL. Our findings may help improve the assessment of disease prognosis and provide potential therapeutic strategies for DLBCL., Competing Interests: Declarations. Conflict of interest: The authors have declared no conflict of interest. Ethical Approval: Every experiment in this study was approved by the Medical Ethics Committee of Shandong Provincial Hospital. Consent to Participant: Ethics approval and consent to participate number: 2021–186. Every action taken complied with the requirements of the Declaration of Helsinki. Informed consent was given by each volunteer. Consent for Publication: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Current literatures suggest a growing body of evidence highlighting the pivotal role of Immunogenic Cell Death (ICD) in multiple tumor types. Nevertheless, the potential and mechanisms of ICD in diffuse large B-cell lymphoma (DLBCL) remain inadequately studied. To address this gap, our current study aims to examine the impact of ICD on DLBCL and identify a corresponding gene signature in DLBC. Using the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Next, univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. Subsequently, the CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients. These findings suggest that the immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. An 8-gene ICD-related signature was identified and validated to prognosticate and evaluate the tumor immune microenvironment in DLBCL. Similarly, the high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50. In conclusion, the present study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor., Competing Interests: Declarations. Conflict of interest: Authors declare no conflicts of interest. Ethical Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2 / BCL6 / c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B , was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P <0.01) and double-expressor cases (20/32, 62.5%; P =0.01) compared with the MYD88 / CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type ( P =0.03), showing poorer outcomes in overall survival ( P =0.02) and progression-free survival ( P =0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The study aimed to assess the role of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) radiomics combined with clinical features using machine learning (ML) in predicting sarcopenia and prognosis of patients with diffuse large B-cell lymphoma (DLBCL)., Methods: A total of 178 DLBCL patients (118 and 60 applied for training and test sets, respectively) who underwent pretreatment 18 F-FDG PET/CT were retrospectively enrolled. Clinical characteristics and PET/CT radiomics features were analyzed, and feature selection was performed using univariate logistic regression and correlation analysis. Sarcopenia prediction models were built by ML algorithms and evaluated. Besides, prognostic models were also developed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified., Results: Fourteen features were finally selected to build sarcopenia prediction and prognosis models, including two clinical (maximum standard uptake value of muscle and BMI), nine PET (seven gray-level and two first-order), and three CT (three gray-level) radiomics features. Among sarcopenia prediction models, combined clinical-PET/CT radiomics features models outperformed other models; especially the support vector machine algorithm achieved the highest area under curve of 0.862, with the sensitivity, specificity, and accuracy of 79.2, 83.3, and 78.3% in the test set. Furthermore, the consistency index based on the prognostic models was 0.753 and 0.807 for PFS and OS, respectively. The enrolled patients were subsequently divided into high-risk and low-risk groups with significant differences, regardless of PFS or OS ( P  < 0.05)., Conclusion: ML models incorporating clinical and PET/CT radiomics features could effectively predict the presence of sarcopenia and assess the prognosis in patients with DLBCL., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The patient was diagnosed with amyopathic dermatomyositis complicated with interstitial pneumonia (IP) at age 35. She had been treated with prednisolone and maintained on tacrolimus (TAC) + azathioprine (AZA). Eight years later, she experienced epigastric pain, and esophagogastroduodenoscopy (EGD) led to a diagnosis of duodenal ulcer. The pain did not improve, so she visited our hospital, where she presented with malaise, anemia, and weight loss. An EGD revealed submucosal tumor-like protrusions in the anterior and posterior walls of the gastric antrum and punched-out ulcers with auricle-like marginal swelling on the inside of the protrusions. Irregular-shaped punched-out ulcers were also observed in the duodenal bulb. Lymphoma was suspected, and biopsy was performed. Histopathology showed diffuse large, atypical lymphocytes with enlarged nuclei, and immunohistochemical staining revealed CD20-positive cells. Diffuse large B cell lymphoma (DLBCL) was diagnosed, which was considered as lymphomas arising in immune deficiency/dysregulation. After discontinuing TAC + AZA for three months, the gastrointestinal symptoms improved, and on EGD, the duodenal lesions had disappeared, with only a shallow depression covered with regenerated epithelium remaining in the posterior wall of the gastric antrum. Seven months later, the patient underwent follow-up EGD, and the disappearance of lymphoma cells was confirmed histopathologically by biopsy. Repeated and detailed endoscopic examination should be considered in an immunosuppressed patient with treatment-resistant gastric or duodenal ulcers., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. Japanese Society of Gastroenterology.)

Synchronous lymphoma (SL) is the simultaneous occurrence of two or more unique kinds of lymphomas in the same individual at the initial diagnosis. Accurate diagnosis requires histopathological examination, immunohistochemistry (IHC), and molecular studies. We found only a handful of reported cases of SLs involving different anatomical sites in medical literature, and no large-scale studies have specifically addressed the frequency of this combination. Given the rarity of this combination, each case is often reported as a unique case study, and treatment approaches may vary depending on individual circumstances. Here, we report a case of a 60-year-old female patient presenting with pain in the abdomen, vomiting, fever, significant weight loss, and palpable inguinal nodes. Her endoscopic biopsy from the stomach revealed diffuse large B-cell lymphoma (DLBCL) while the inguinal node biopsy showed classical Hodgkin lymphoma (cHL), mixed cellularity type. Our report discusses and highlights the importance of detailed clinical history, investigations, and molecular workups that are essential to diagnosing these rare cases., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Rana et al.)

Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and a sizable fraction of the DLBCL patients presents with advanced, relapsed, and refractory disease, demonstrating poor response to standard chemotherapy regimens. Radioimmunotherapy (RIT) has shown to be clinically effective in refractory DLBCL. We present the case of a patient with DLBCL with [18F]FDG-avid widespread skeletal as well as splenic involvement as poor prognostic extranodal disease on FDG PET/CT. RIT based on [177Lu]Lu-DOTA-rituximab was explored to study the biodistribution and dosimetry of [177Lu]Lu-DOTA-rituximab in CD20-positive lymphoma. An exceptionally high tracer concentration in skeletal and splenic disease was observed, supporting its potential RIT application in relapsed and refractory DLBCL patients in the future., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive forms of non-Hodgkin's lymphoma. This study aimed to evaluate the performance of the abbreviated Comprehensive Geriatric Assessment (aCGA) in assessing frailty and predicting clinical outcomes in elderly patients with DLBCL., Methods: A total of 91 patients aged ≥ 65 years with newly diagnosed DLBCL and who received immunochemotherapy at a single medical center in Taiwan between August 2019 and December 2022 were prospectively enrolled. Frailty was assessed in all participating patients within seven days of the first cycle of immunochemotherapy. The primary objective was to compare aCGA's accuracy in assessing frailty with that of the full CGA. Secondary objectives included assessing correlations between frailty and severe adverse events (sAEs), early mortality, and overall survival (OS)., Results: In the cohort, 50 (55%) and 38 (42%) patients were categorized as frail based on CGA and aCGA, respectively. A high number of aCGA domains impairment were positively associated with a high number of CGA domains impairment. The receiver operating characteristic for aCGA for detecting frailty was 0.846 (95% confidence interval [CI], 0.756-0.926). A cut-off point of ≥ 2 aCGA domain impairments indicated frailty, with a sensitivity of 70.0% and specificity of 92.7%. Based on aCGA, the early mortality rate was 7.5% and 26.3% (p = 0.019) for fit and frail patients, respectively. The 1-year and 2-year OS rates were 77.7% and 67.4% for fit patients, and 57.1% and 45.4% for frail patients, respectively. The adjusted hazard ratio for OS was 2.42 (95% CI, 1.06-5.49, p = 0.035) for frail patients compared to fit patients., Conclusions: This finding suggested that aCGA could be used as an efficient alternative to the full CGA, potentially improving the clinical management and treatment decision-making for elderly patients with DLBCL., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer., Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes., Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly for diffuse large B-cell lymphoma., Conclusions: These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There are some evidences that hypogammaglobulinemia in newly diagnosed diffuse large B cell lymphoma (DLBCL) is a predictor for inferior outcome, but the risk for infection-related admissions specifically related to hypogammaglobulinemia is not known. The aim was to explore if hypogammaglobulinemia in untreated DLBCL in a Swedish cohort was associated with inferior outcome, and to assess the relationship between low immunoglobulin (Ig) levels and infections. Using data from the Swedish Lymphoma Register, we retrospectively identified patients above18 years diagnosed with DLBCL, receiving anthracycline-based curative therapy during 2000-2015 in Southern Sweden with Ig-levels tested at baseline. Data on Ig levels and infections were collected from medical records. Five hundred eighty-five patients were included, median age was 69 years. Hypogammaglobulinemia was detected at baseline in 24%, the most common Ig deficiency was IgG (18%), followed by IgA (10%) and IgM (8%). Hypogammaglobulinemia was associated with inferior overall survival (HR 1.4, 95% CI 1.0-1.8, p-value 0.018), but not when adjusted for International Prognostic Index (IPI). Low levels of Ig were associated with more infections during lymphoma treatment (p-value 0.013), also when adjusted for IPI (p-value < 0.001). Among patients with IgG deficiency, 47% had ≥ 1 infections versus 35% in patients with normal IgG (HR 1.2, p = 0.025). In conclusion, hypogammaglobulinemia was a frequent finding in patients with newly diagnosed DLBCL, with clinical impact in terms of treatment complications and outcome., (© 2024 John Wiley & Sons Ltd.)

MYD88 L265P mutation is a gain-of-function driver mutation. It is observed in a significant proportion of Waldenstrom macroglobulinemia and activated B-cell subtype of diffuse large B-cell lymphoma (DLBCL; non-germinal center subtype). The incidence of this mutation in the subtypes of DLBCL has not yet been documented in the Pakistani population. This study aimed to ascertain the frequency and association of MYD88 L265P mutation within 2 subtypes of DLBCL, germinal center B-cell-like (GCB) and non-GCB B-cell lymphoma (non-GCB), in the local population. This cross-sectional study was conducted at the Armed Forces Institute of Pathology, Punjab, Pakistan. All newly diagnosed cases of DLBCL were included in the study. We analyzed 82 biopsy-proven cases of DLBCL (28 cases of GCB subtype and 54 cases of non-GCB subtype). DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and a conventional polymerase chain reaction was used to detect the MYD88 L265P mutation. The MYD88 L265P mutation was detected in 01 of 28 (3.6%) cases of the GCB subtype (95% CI: 0%-10%) and in 12 of 54 (22.2%) cases of the non-GCB subtype (95% CI: 11%-33%). Pearsos χ2 test revealed a statistically significant association of MYD88 L265P mutation with non-GCB subtype of DLBCL (P = 0.024). This association will assist in identifying a target population that may benefit from MYD88-specific treatment regimens. This may exponentially improve the outcome of patients with DLBCL harboring this mutation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group, 89.2% of CT-group and 78.8% of no-bridge-group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT-group, 28.2% in the CT-group, and 47.6% in the no-bridge-group (p = 0.044, CT-bridging vs RT-bridging); 1-year OS was 86.7% in the RT-group, 52.7% in the CT-group and 69% in the no-bridge-group (p = 0.025, CT-bridging vs RT-bridging). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT-group, 3.3% RT-group, 7.7% no-bridge group; p = 0.05). In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site., Competing Interests: Competing interests: The authors decalre no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease group. Ibrutinib's monotherapy or combination therapy is effective in relapsed/refractory (R/R) DLBCL. However, the treatment response in R/R DLBCL varies from 15% to 90% with different regimens, and the tolerance remains controversial., Areas of Uncertainty: The efficacy and safety of ibrutinib monotherapy or combination therapy in patients with R/R DLBCL remain uncertain., Data Sources: The PubMed, CBM, MEDLINE, Cochrane Library, and Embase databases were searched from their inception to July 2021., Therapeutic Advances: The total complete remission rate (CRR) and overall response rate in R/R DLBCL patients treated with ibrutinib were 26% and 49%, respectively. The CRR of ibrutinib combination therapy was significantly higher than the ibrutinib monotherapy (45% vs. 19%). Moreover, the CRR of patients was 40% in double expressing lymphoma, 35% in central nervous system lymphoma, and 33% in nongerminal center B-cell-like (non-GCB) DLBCL, which was higher than the 8% in those with the GCB subtype. The pooled median PFS and overall survival were 5.57 and 10.17 months, respectively. GCB-DLBCL had the worst overall survival (5.1 months). Nevertheless, we found that combination regimens had no survival advantage compared with monotherapy ( P > 0.05), indicating that combination therapy was only a transitional treatment and bridge for chimeric antigen receptor T cells or other treatments. Moreover, 12% of patients on ibrutinib combination therapy had ≥grade 3 adverse events compared with 9% on ibrutinib monotherapy., Conclusions: Ibrutinib monotherapy or combination therapy was safe and effective in treating R/R DLBCL with tolerable adverse reactions., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The purpose of this study was to comprehensively analyze the prediction role of NADPH oxidase (NOX)-related polymorphisms (NCF4: rs1883112, CYBA: rs4673, RAC2: rs13058338) and immunohistochemical indices on survival in diffuse large B-cell lymphoma (DLBCL).The impact of NOX polymorphisms were evaluated in 335 DLBCL patients treated with R (rituximab)-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) from Harbin Medical University Cancer Hospital. We also collected information on their immunohistochemical expression and clinical outcomes.Among the patients treated with R-CHOP therapy, the patients with CyclinD1 (+) had significantly shorter progression-free survival (PFS) (p = 0.001) and event-free survival (EFS) (p < 0.001) than CyclinD1 (-) patients. Among patients received CHOP therapy, PFS was significantly longer in CD20 (+) patients (p = 0.011) than in CD20(-) patients. Among the patients treated with R-CHOP therapy, the PFS (p = 0.020) and EFS (p < 0.001) of patients with NCF4 rs1883112 AA/AG genotype were significantly longer than the patients with GG genotype. Patients treated with R-CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher myelosuppression compared to patients with TT genotype (p = 0.027). Patients treated with CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher systemic adverse events (p = 0.029). Cox regression analysis showed that NCF4 rs1883112 GG genotype and CyclinD1 (+) were the factors contributing to the poor outcomes in DLBCL patients treated with R-CHOP therapy.In conclusion, the results suggested that the NCF4 rs1883112 G allele may be a poor prognostic biomarker, especially for the DLBCL patients with CD3(-), CD5 (-), CD10 (-), Bcl-2 (+), Bcl-6 (+) or Ki-67(%) < 80%., Competing Interests: Declarations. Ethical approval: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Ethics Committee of Harbin Medical University (HMUIRB20160004)) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, with significant clinical heterogeneity. Recent studies suggest that the intratumoral microbiome may influence the tumor microenvironment, affecting patient prognosis and therapeutic responses. This study aims to identify microbiome-related subtypes in DLBCL and assess their impact on prognosis, immune infiltration, and therapeutic sensitivity., Methods: Transcriptomic and microbiome data from 48 DLBCL patients were obtained from public databases. Consensus clustering was used to classify patients into distinct microbiome-related subtypes. Functional enrichment analysis, immune infiltration assessments, and single-cell RNA sequencing were performed to explore the biological characteristics of these subtypes. Drug sensitivity predictions were made using the OncoPredict tool. Hub genes' expression and biological function were validated and inferred in cell lines and independent cohorts of DLBCL., Results: Two distinct microbiome-related subtypes were identified. Patients in Cluster 1 exhibited significantly better overall survival (P < 0.05), with higher immune infiltration of regulatory T cells and M0 macrophages compared to Cluster 2, which was associated with poorer outcomes. Functional enrichment analysis revealed that genes in Cluster 1 were involved in immune regulatory pathways, including cytokine-cytokine receptor interactions and chemokine signaling, suggesting enhanced anti-tumor immune responses. In contrast, genes in Cluster 2 were enriched in immunosuppressive pathways, contributing to a less favorable prognosis. Single-cell RNA sequencing analysis revealed significant heterogeneity in immune cell populations within the tumor microenvironment. B cells exhibited the most notable heterogeneity, as indicated by stemness and differentiation potential scoring. Intercellular communication analysis demonstrated that B cells played a key role in immune cell interactions, with significant differences observed in MIF signaling between B-cell subgroups. Pseudo-time analysis further revealed distinct differentiation trajectories of B cells, highlighting their potential heterogeneity across different immune environments. Metabolic pathway analysis showed significant differences in the average expression levels of metabolic pathways among B-cell subgroups, suggesting functional specialization. Furthermore, interaction analysis between core genes involved in B-cell differentiation and microbiome-driven differentially expressed genes identified nine common genes (GSTM5, LURAP1, LINC02802, MAB21L3, C2CD4D, MMEL1, TSPAN2, and CITED4), which were found to play critical roles in B-cell differentiation and were influenced by the intratumoral microbiome. DLBCL cell lines and clinical cohorts validated that MMEL1 and CITED4 with important biologically function in DLBCL cell survival and subtype classification., Conclusions: This study demonstrates the prognostic significance of the intratumoral microbiome in DLBCL, identifying distinct microbiome-related subtypes that impact immune infiltration, metabolic activity, and therapeutic responses. The findings provide insights into the immune heterogeneity within the tumor microenvironment, focusing on B cells and their differentiation dynamics. These results lay the foundation for microbiome-based prognostic biomarkers and personalized treatment approaches, ultimately aiming to enhance patient outcomes in DLBCL., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable., (© 2025. The Author(s).)

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis and frequent central nervous system (CNS) relapse. Sandwich therapy comprising dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy and manageable safety in a phase II study of patients diagnosed with stage II-IV CD5+ DLBCL. To validate the results of that study and elucidate the current state of treatment for CD5+ DLBCL, we retrospectively analyzed the outcomes of patients with CD5+ DLBCL diagnosed between 2016 and 2021 who received anthracycline-containing chemotherapy with rituximab. Among the 346 patients evaluated, 62 (18%) received DA-EPOCH-R/HD-MTX. The median follow-up time was 43 months. In 55 patients with stage II-IV disease treated with DA-EPOCH-R/HD-MTX, the 2-year overall survival (OS), progression-free survival, and cumulative incidence of CNS relapse were 87% (95% CI, 73%-94%), 76% (95% CI, 61%-86%), and 7.3% (95% CI, 2.4%-16%), respectively. There were no treatment-related deaths. Febrile neutropenia occurred in 18 (33%) patients. Multivariate analysis of the 346 patients identified elevated serum lactate dehydrogenase levels, multiple extranodal involvement, no intrathecal MTX (IT-MTX), and no DA-EPOCH-R/HD-MTX as independent risk factors for OS. Only one CNS relapse event was observed in 28 patients who received both HD-MTX and IT-MTX. Our study provides real-world data on the treatments and outcomes of a large number of patients. The favorable survival and manageable toxicity of DA-EPOCH-R/HD-MTX have been validated in clinical settings. The use of HD-MTX and IT-MTX might be effective for preventing CNS relapse in patients with CD5+ DLBCL., (© 2025 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Background: Primary central nervous system lymphoma (PCNSL) carries a poor prognosis. Radiomics may hold potential value in prognostic assessment., Purpose: To develop and validate an MRI-based radiomics model and combine it with clinical factors to assess progression-free survival (PFS) and overall survival (OS) of patients with PCNSL., Study Type: Retrospective and prospective., Population: Three hundred seventy-nine patients (179 female, 53 ± 7 years) from 2014 to 2022., Field Strength/sequence: T2/fluid-attenuated inversion recovery, contrast-enhanced T1WI and diffusion-weighted echo-planar imaging sequences on 3.0 T., Assessment: Radiomics features were extracted from enhanced tumor regions on preoperative multi-sequence MRI. Using a least absolute shrinkage and selection operator (LASSO) Cox regression model to select radiomic signatures in training cohort (N = 169). Cox proportional hazards models were constructed for clinical, radiomics, and combined models, with internal (N = 72) and external (N = 32) cohorts validating model performance., Statistical Tests: Chi-squared, Mann-Whitney, Kaplan-Meier, log-rank, LASSO, Cox, decision curve analysis, time-dependent Receiver Operating Characteristic, area under the curve (AUC), and likelihood ratio test. P-value <0.05 was considered significant., Results: Follow-up duration was 28.79 ± 22.59 months (median: 25). High-risk patients, determined by the median radiomics score, showed significantly lower survival rates than low-risk patients. Compared with NCCN-IPI, conventional imaging and clinical models, the combined model achieved the highest C-index for both PFS (0.660 internal, 0.802 external) and OS (0.733 internal, 0.781 external) in validation. Net benefit was greater with radiomics than with clinical alone. The combined model exhibited performance with AUCs of 0.680, 0.752, and 0.830 for predicting 1-year, 3-year, and 5-year PFS, and 0.770, 0.789, and 0.863 for OS in internal validation, with PFS AUCs of 0.860 and 0.826 and OS AUCs of 0.859 and 0.748 for 1-year and 3-year survival in external validation., Data Conclusion: Incorporating a multi-sequence MR-based radiomics model into clinical models enhances the assess accuracy for the prognosis of PCNSL., Evidence Level: 4 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma subtype, relapses or becomes refractory (R/R) in 40 % of cases after initial treatment. Among the second-line treatments for these patients is CAR T-cell therapy, which is considered the gold standard and treatment better than SCT. For these patients, polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) is a novel treatment. The main goal of our research is to evaluate Pola-BR's efficacy in R/R DLBCL patients., Methods: We followed PRISMA criteria for conducting this systematic review and meta-analysis. A search was conducted from the start until May 2024 using the Cochrane Library, PubMed, and clinicaltrials.gov. Studies included randomized-controlled trials, observational studies, and single-arm studies assessing Pola-BR efficacy in R/R DLBCL patients. The overall response rate (ORR), partial response (PR), and complete response (CR) were the main outcomes. Using random-effect models, statistical analysis was carried out on OpenMeta[Analyst] software leading to pooled risk ratios with 95 % confidence intervals (CIs)., Results: Eight studies with 398 patients were present in our study. The studies were of high quality, with pooled analysis showing a significant ORR of 52.6 % (95 % CI: 43.6 - 61.6 %), CR of 34.3 % (95 % CI: 23.5 - 45.0 %), and PR of 15.5 % (95 % CI: 8.7 - 22.3 %). Significant hematologic toxicities were observed, the most common being, neutropenia, thrombocytopenia, neuropathy, and anemia., Conclusion: Pola-BR is an effective option for advanced R/R DLBCL but poses significant hematologic toxicity, requiring careful management. Further high-quality randomized trials are needed to better understand and evaluate Pola-BR's success. To fully assess its effectiveness, comparisons with non-cell therapies are essential., Competing Interests: Declaration of Competing Interest The authors of the manuscript do not have any conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, which characterized by a high degree of heterogeneity in terms of clinical presentation, molecular phenotype, and genetic features. However, approximately 30 %-40 % of patients are refractory to standard chemotherapy, and their prognosis is poor. The emergence of small-molecule inhibitors, such as Bruton's tyrosine kinase inhibitors (BTKi), has greatly improved the treatment of DLBCL; however, drug resistance associated with small-molecule inhibitors has greatly limited their clinical application. In this study, we elucidated the principal genes influencing BTKi sensitivity in DLBCL and delineated the underlying mechanisms. This study identified cyclin-dependent kinase 1 (CDK1) as the central gene influencing BTKi sensitivity in DLBCL cells. The application of RO-3306 effectively promoted the growth and increased the apoptotic rate of DLBCL cells. Furthermore, RO-3306 increased the susceptibility of DLBCL cells to BTKis in both in vitro and xenograft experimental models. RNA-seq analyses suggested the potential modulation of the JAK2/STAT3 signaling cascade by RO-3306, a finding further confirmed by the diminished phosphorylation documented by western blotting. This study provides pivotal insights into the mechanisms governing BTKi sensitivity in DLBCL and potentially reveals new avenues for targeted therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Introduction: Ferroptosis is a recently identified iron-dependent programmed cell death closely linked to the progression of diffuse large B-cell lymphoma (DLBCL). While studies have shown that FA-2-b-β extracted from Agaricus blazei Murill affects various malignancies, its specific role in modulating ferroptosis in DLBCL and the underlying mechanisms are not yet clear., Objectives: This study aims to elucidate the anticancer properties and mechanisms of FA-2-b-β in inducing ferroptosis in DLBCL cells., Methods: The cell counting kit 8 assay was carried out to evaluate the inhibition of cellular proliferation. Ferroptosis was evaluated using the ferrous colorimetric method, together with kits for measuring malondialdehyde (MDA), reduced glutathione (GSH), reactive oxygen species (ROS), western blotting, JC-1 assays, and transmission electron microscopy. Reverse transcriptionquantitative polymerase chain reaction and western blot were conducted to determine whether FA- 2-b-β affected nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase 1 (HO-1)., Results: FA-2-b-β induced ferroptosis in DLBCL cells by elevating the ROS and MDA levels, facilitating the accretion of Fe²⁺, diminishing GSH, upregulating the expression of PTGS2, and downregulating the expression of FTH1, SLC7A11, and GPX4. Furthermore, FA-2-b-β caused structural damage to mitochondria and diminished the mitochondrial membrane potential. The ferroptosis triggered by FA-2-b-β also led to the downregulation of Nrf2 and HO-1, thereby regulating the Nrf2/HO-1 pathway., Conclusion: FA-2-b-β suppressed DLBCL cell growth by inducing ferroptosis through the Nrf2/HO-1 pathway, making it an attractive potential therapeutic option., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The prognostic value of models such as the international prognostic index (IPI) in patients with malignant lymphomas treated with a combination of rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone is well established. However, whether these prognostic models apply to patients treated with a combination of tetrahydropyranyl adriamycin, rituximab, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) is unclear. This retrospective analysis included 101 patients with Diffuse large B-cell lymphoma (DLBCL) treated with R-THP-COP. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), complete response rate (CRR), and effectiveness of risk prediction in the IPI, revised international prognostic index (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI groups. OS and PFS at 5 years were 67% and 58.9%. CRR was 63.5%. The IPI, R-IPI, and NCCN-IPI predicted the outcomes of patients treated with R-THP-COP. According to the NCCN-IPI, OS and PFS could distinguish four risk groups. In conclusion, the NCCN-IPI is the most effective prognostic tool for identifying patients with poor prognosis, even those treated with R-THP-COP.

Background: Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy with diverse patient outcomes, largely influenced by the tumor microenvironment (TME). Understanding the roles of fibroblasts and macrophages within the TME is essential for developing personalized therapeutic strategies in DLBCL., Methods: This study is a multi-omics approach, integrating spatial transcriptomics (n = 11), bulk transcriptomics (n = 2,499), immunohistochemistry (IHC, n = 37), multiplex immunofluorescence (mIF, n = 56), and plasma samples (n = 240) to identify and characterize fibroblast and tumor-associated macrophage subtypes in the TME. Hub genes for LYZ + fibroblasts and FN1 + macrophages were selected through univariate Cox regression and random forest analyses. Their prognostic significance was validated using IHC, mIF, and autoantibody assays in DLBCL patients treated with R-CHOP and in non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs)., Results: Fibroblasts and macrophages were classified into two distinct subtypes. Patients with higher LYZ + fibroblasts infiltration demonstrated superior prognosis, which was associated with increased infiltration of FN1 + macrophages. Key hub genes identified for LYZ + fibroblasts included LYZ, ANPEP, CSF3R, C15orf48, LILRB4, CLEC7A, and COL7A1, while hub FN1 + macrophages genes included COL1A1, FN1, APOE, DCN, MMP2, SPP1, COL3A1, and COL1A2. Independent prognostic markers in DLBCL treated with R-CHOP and NSCLC treated with ICIs were identified, including LYZ and LILRB4 at both protein and mRNA levels, and COL1A2 autoantibodies (p < 0.05). In DLBCL patients treated with R-CHOP, FN1 mRNA and autoantibody levels were also prognostic markers (p < 0.05). In NSCLC treated with ICIs, COL3A1 autoantibody was prognostic marker (p < 0.05)., Conclusions: This study identified a prognostically relevant LYZ + fibroblasts and FN1 + macrophages in DLBCL. The hub genes associated with these subtypes represent potential biomarkers, providing insights into improving patient outcomes in DLBCL., Competing Interests: Declarations. Conflict of interests: The authors report there are no competing interests to declare. All authors agreed to submit for consideration for publication in this journal. Ethical approval and consent to participate: This study has been approved by the Ethics Committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (No. 23/262-4004 and No.22/486-3688). All experiments were executed according to the Declaration of Helsinki. Consent for publication: All authors agreed to submit for consideration for publication in this journal., (© 2025. The Author(s).)