{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:09:54Z","timestamp":1785424194751,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/2\/3\/48\/2018\/Online Onco Fship\/NCD-III"],"award-info":[{"award-number":["3\/2\/3\/48\/2018\/Online Onco Fship\/NCD-III"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"award":["3\/2\/3\/48\/2018\/Online Onco Fship\/NCD-III"],"award-info":[{"award-number":["3\/2\/3\/48\/2018\/Online Onco Fship\/NCD-III"]}],"id":[{"id":"https:\/\/ror.org\/0492wrx28","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016724","name":"PGIMER\u2014Institute Research Grant","doi-asserted-by":"publisher","award":["71\/6-Edu\/13\/1471"],"award-info":[{"award-number":["71\/6-Edu\/13\/1471"]}],"id":[{"id":"10.13039\/100016724","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin\u2019s lymphoma (NHL), accounting for 30\u201340% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-\u03b2, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal\/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor\u2013stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL.<\/jats:p>","DOI":"10.3390\/cancers18111697","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"1697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenic Mutations in the Tumor Microenvironment Drive Tumor Progression in Diffuse Large B-Cell Lymphoma Through Tumor\u2013Stroma Cross-Talk"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-3479","authenticated-orcid":false,"given":"Vaishali","family":"Aggarwal","sequence":"first","affiliation":[{"name":"Molecular Biology Laboratory, Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"},{"name":"Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanjit","family":"Bal","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-8491","authenticated-orcid":false,"given":"Pankaj","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash","family":"Varma","sequence":"additional","affiliation":[{"name":"Department of Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"},{"name":"Internal Medicine, Fortis Hospital, Mohali 160062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashim","family":"Das","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India"},{"name":"Department of Hepatopathology, Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar 751024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s12672-025-01958-w","article-title":"Diffuse large B cell lymphoma (DLBCL): Epidemiology, pathophysiology, risk stratification, advancement in diagnostic approaches and prospects: Narrative review","volume":"16","author":"Berhan","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1053\/j.seminhematol.2023.11.004","article-title":"Epidemiology and etiology of diffuse large B-cell lymphoma","volume":"60","author":"Wang","year":"2023","journal-title":"Semin. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, L., Li, Q., Niu, R., Sun, W., and Liang, H. (2025). Single-cell RNA sequencing in diffuse large B-cell lymphoma: Tumor heterogeneity, microenvironment, resistance, and prognostic markers. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1583250"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1007\/s00277-024-05880-z","article-title":"Advances in biology, diagnosis and treatment of DLBCL","volume":"103","author":"Shi","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110713","DOI":"10.1016\/j.celrep.2022.110713","article-title":"A single-cell atlas of diffuse large B cell lymphoma","volume":"39","author":"Ye","year":"2022","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/hon.2512","article-title":"Refractory diffuse large B-cell lymphoma after first-line immuno-CT: Treatment options and outcomes","volume":"36","author":"Bourbon","year":"2018","journal-title":"Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/hon.2613","article-title":"Frontline treatment of diffuse large B-cell lymphoma: Beyond R-CHOP","volume":"37","author":"Mondello","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_8","first-page":"1912","article-title":"Analysis of Relevant Factors of Refractory and Relapse DLBCL Treated by Rituximab Combined with CHOP\/EPOCH Regimen","volume":"28","author":"Zhang","year":"2020","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1038\/s41375-021-01285-3","article-title":"Treatment resistance in diffuse large B-cell lymphoma","volume":"35","author":"He","year":"2021","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/j.1365-2141.2008.07218.x","article-title":"Gene expression profiling of diffuse large B-cell lymphoma supervised by CD21 expression","volume":"142","author":"Miyazaki","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41591-018-0016-8","article-title":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","volume":"24","author":"Chapuy","year":"2018","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Berendsen, M.R., Stevens, W.B.C., van den Brand, M., van Krieken, J.H., and Scheijen, B. (2020). Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance. Cancers, 12.","DOI":"10.3390\/cancers12123553"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8586354","DOI":"10.1155\/2019\/8586354","article-title":"Tumor Microenvironment in Diffuse Large B-Cell Lymphoma: Role and Prognosis","volume":"2019","author":"Cioroianu","year":"2019","journal-title":"Anal. Cell Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mulder, T.A., Wahlin, B.E., Osterborg, A., and Palma, M. (2019). Targeting the Immune Microenvironment in Lymphomas of B-Cell Origin: From Biology to Clinical Application. Cancers, 11.","DOI":"10.3390\/cancers11070915"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa0802885","article-title":"Stromal gene signatures in large-B-cell lymphomas","volume":"359","author":"Lenz","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"151","DOI":"10.20892\/j.issn.2095-3941.2017.0007","article-title":"Significance of stromal-1 and stromal-2 signatures and biologic prognostic model in diffuse large B-cell lymphoma","volume":"14","author":"Abdou","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00277-026-06828-1","article-title":"Machine learning based on clinical and gene expression data assists in survival prediction and treatment optimization for diffuse large B-Cell lymphoma patients","volume":"105","author":"Lin","year":"2026","journal-title":"Ann. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41408-020-00404-0","article-title":"Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma","volume":"11","author":"Merdan","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1093\/annonc\/mdy450","article-title":"Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue","volume":"29","author":"Ciavarella","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_20","first-page":"522","article-title":"Dasatinib Is Preferentially Active in the Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma","volume":"18","author":"Cann","year":"2019","journal-title":"J. Prot. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1182\/blood.2023021002","article-title":"Genetic mechanisms underlying tumor microenvironment composition and function in diffuse large B-cell lymphoma","volume":"143","author":"Cerchietti","year":"2024","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70602","DOI":"10.1002\/cam4.70602","article-title":"A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features","volume":"14","author":"Zhou","year":"2025","journal-title":"Cancer Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"key":"ref_26","unstructured":"Rimsza, L., Lister, A.T., Chan, W.C., Weisenburger, D., Delabie, J., Smeland, E.B., Holte, H., Kvaloy, S., Braziel, R.M., and Fisher, R.I. (2018). Survival Predictor for Diffuse Large B Cell Lymphoma. (Google Patents US-9970059-B2)."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/0091-7435(89)90033-9","article-title":"Cancer chemoprevention by supplemental carotenoids in animals and humans","volume":"18","author":"Santamaria","year":"1989","journal-title":"Prev. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10324","DOI":"10.1158\/0008-5472.CAN-08-2582","article-title":"A mutant collagen XIII alters intestinal expression of immune response genes and predisposes transgenic mice to develop B-cell lymphomas","volume":"68","author":"Tuomisto","year":"2008","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Alinezhad, S., Vaananen, R.M., Mattsson, J., Li, Y., Tallgren, T., Tong Ochoa, N., Bjartell, A., Akerfelt, M., Taimen, P., and Bostrom, P.J. (2016). Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158255"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6452","DOI":"10.1158\/1078-0432.CCR-14-1236","article-title":"Clever-1\/stabilin-1 controls cancer growth and metastasis","volume":"20","author":"Karikoski","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_31","first-page":"1625","article-title":"Expression of stabilin-1 in M2 macrophages in human granulomatous disease and melanocytic lesions","volume":"7","author":"Schonhaar","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1158\/0008-5472.CAN-15-0024","article-title":"Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression","volume":"75","author":"Hurley","year":"2015","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1093\/hmg\/ddu749","article-title":"Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing","volume":"24","author":"Kunstman","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.1038\/ncomms7604","article-title":"Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia","volume":"6","author":"Ma","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Parry, M., Rose-Zerilli, M.J., Gibson, J., Ennis, S., Walewska, R., Forster, J., Parker, H., Davis, Z., Gardiner, A., and Collins, A. (2013). Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083244"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14977","DOI":"10.1073\/pnas.1203525109","article-title":"Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome","volume":"109","author":"Hurley","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","first-page":"278","article-title":"Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated protein is down regulated in gastric adenocarcinoma","volume":"7","author":"Jakharia","year":"2016","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.molonc.2013.07.008","article-title":"SPARCL1 suppresses metastasis in prostate cancer","volume":"7","author":"Xiang","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/j.1750-3639.2010.00399.x","article-title":"Extracellular matrix in multiple sclerosis lesions: Fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells","volume":"20","author":"Mohan","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Reis, P.P., Waldron, L., Goswami, R.S., Xu, W., Xuan, Y., Perez-Ordonez, B., Gullane, P., Irish, J., Jurisica, I., and Kamel-Reid, S. (2011). mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol., 11.","DOI":"10.1186\/1472-6750-11-46"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mirzapoiazova, T., Mambetsariev, N., Lennon, F.E., Mambetsariev, B., Berlind, J.E., Salgia, R., and Singleton, P.A. (2015). HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression. Front. Oncol., 5.","DOI":"10.3389\/fonc.2015.00164"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tomsic, J., Fultz, R., Liyanarachchi, S., He, H., Senter, L., and de la Chapelle, A. (2016). HABP2 G534E Variant in Papillary Thyroid Carcinoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146315"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Weeks, A.L., Wilson, S.G., Ward, L., Goldblatt, J., Hui, J., and Walsh, J.P. (2016). HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0323-1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.tvjl.2015.08.011","article-title":"Developmental pathways and endothelial to mesenchymal transition in canine myxomatous mitral valve disease","volume":"206","author":"Lu","year":"2015","journal-title":"Vet. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1134\/S0026893307040061","article-title":"Novel methylation and expression markers associated with breast cancer","volume":"41","author":"Kuznetsova","year":"2007","journal-title":"Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/humu.22333","article-title":"Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer","volume":"34","author":"Smith","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s00262-001-0232-8","article-title":"T-helper (Th)1\/Th2 imbalance in patients with previously untreated B-cell diffuse large cell lymphoma","volume":"50","author":"Mori","year":"2001","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1158\/1055-9965.EPI-09-1237","article-title":"Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): A case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition","volume":"19","author":"Krop","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3109\/10428190009059274","article-title":"Tumour necrosis factor gene polymorphisms in lymphoproliferative disease","volume":"38","author":"Dickinson","year":"2000","journal-title":"Leuk. Lymphoma"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: Ffates, functions, and faults","volume":"112","author":"Zhu","year":"2008","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0161-5890(02)00210-9","article-title":"The two faces of IL-6 on Th1\/Th2 differentiation","volume":"39","author":"Diehl","year":"2002","journal-title":"Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cytogfr.2011.02.003","article-title":"IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer","volume":"22","author":"Neurath","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e10576","DOI":"10.15252\/emmm.201910576","article-title":"The IL-6 signaling complex is a critical driver, negative prognostic factor, and therapeutic target in diffuse large B-cell lymphoma","volume":"11","author":"Hashwah","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1089\/jir.2020.0111","article-title":"Novel Interleukin-6 Inducible Gene PDZ-Binding Kinase Promotes Tumor Growth of Multiple Myeloma Cells","volume":"40","author":"Ota","year":"2020","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1097\/00000421-200212000-00007","article-title":"Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin\u2019s lymphoma","volume":"25","author":"Aydin","year":"2002","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1182\/blood-2003-06-1850","article-title":"Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma","volume":"103","author":"Baseggio","year":"2004","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1751-553X.2007.00951.x","article-title":"Correlation of serum IL-6, IL-8 and IL-10 levels with clinicopathological features and prognosis in patients with diffuse large B-cell lymphoma","volume":"30","author":"Stifter","year":"2008","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1365-2141.2005.05393.x","article-title":"Serum levels of inflammatory cytokines at diagnosis correlate to the bcl-6 and CD10 defined germinal centre (GC) phenotype and bcl-2 expression in patients with diffuse large B-cell lymphoma","volume":"128","author":"Pedersen","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"186","DOI":"10.7326\/0003-4819-127-3-199708010-00002","article-title":"Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma","volume":"127","author":"Preti","year":"1997","journal-title":"Ann. Intern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1200\/JCO.1995.13.3.575","article-title":"Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma","volume":"13","author":"Seymour","year":"1995","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-0609.1995.tb01619.x","article-title":"Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin\u2019s lymphoma","volume":"54","author":"Stasi","year":"1995","journal-title":"Eur. J. Haematol."},{"key":"ref_62","first-page":"5499","article-title":"Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin\u2019s lymphoma cells and act as cooperative growth factors","volume":"56","author":"Voorzanger","year":"1996","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/10428199709051774","article-title":"Interleukin-10 in non-Hodgkin\u2019s lymphoma","volume":"26","author":"Cortes","year":"1997","journal-title":"Leuk. Lymphoma"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1182\/blood.V82.7.2169.2169","article-title":"Serum interleukin-10 in non-Hodgkin\u2019s lymphoma: A prognostic factor","volume":"82","author":"Blay","year":"1993","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1182\/blood-2005-10-4160","article-title":"Cytokine polymorphisms in the Th1\/Th2 pathway and susceptibility to non-Hodgkin lymphoma","volume":"107","author":"Lan","year":"2006","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/11\/1697\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:28:53Z","timestamp":1780468133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/11\/1697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cancers18111697"],"URL":"https:\/\/doi.org\/10.3390\/cancers18111697","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}