Circulating Exosomal CD30 And CD79B in Diffuse Large B-Cell Lymphoma Patients

Year 2025, Volume: 9 Issue: 3, 593 - 603, 30.09.2025

Cansu Barış Moğul , Sibel Hacıoğlu , Nilay Şen Türk , Vildan Caner , Hande Şenol

https://doi.org/10.30621/jbachs.1727932

Abstract

Project Number

321S005

Circulating Exosomal CD30 And CD79B in Diffuse Large B-Cell Lymphoma Patients

Abstract

Purpose: Up to 30-40% of patients do not respond to treatment or relapse after R-CHOP chemoimmunotherapy in DLBCL. The predictive biomarkers for identifying candidates for new therapies have not been extensively studied. We aimed to determine the presence of CD3, CD19, CD20, CD30 and CD79B in plasma-derived exosomes from DLBCL patients and to compare the profiles of target proteins in exosomes and matched primary tumour tissue.
Material and Methods: Exosome samples from 20 newly diagnosed DLBCL patients and 20 healthy controls from our previous studies were characterized according to the recent MISEV2018 guidelines. The presence of targeted antibodies in exosomes was determined by Western Blotting, while their expression in primary tumour tissue was analysed by immunohistochemistry.
Results: Seventeen (85%) patients had CD30-positive exosomes in their blood, while tumor cells expressing CD30 were found in only 2 (10%) patients. We only evaluated CD79B expression in tumor cells from 6 patients.
Conclusion: In addition to tumor cells, characterising the factors present in the tumor microenvironment that support tumor cells, such as exosomes, will increase our success in treating DLBCL. Preclinical and clinical studies are needed to evaluate the presence of circulating CD30- and CD79B-positive exosomes in the selection of candidates for targeted immunotherapies using a non-invasive approach.

Keywords

Non-Hodgkin Lymphoma , Diffuse Large B-cell Lymphoma , Exosome , CD30 , CD79B

Project Number

321S005

References

• Cheson BD, Nowakowski G, Salles G. Diffuse large B-cell lymphoma: new targets and novel therapies. Blood Cancer J 2021;11(4):68.
• Abramson JS, Ghosh N, Smith SM. ADCs, BiTEs, CARs, and Small Molecules: A New Era of Targeted Therapy in Non-Hodgkin Lymphoma. Am Soc Clin Oncol Educ Book. 2020;40:302-313.
• Batista IA, Quintas ST, Melo SA. The Interplay of Exosomes and NK Cells in Cancer Biology. Cancers (Basel) 2021;13(3):473.
• Ling HY, Yang Z, Wang PJ, Sun Y, Ju SG, Li J, et al. Diffuse large B-cell lymphoma-derived exosomes push macrophage polarization toward M2 phenotype via GP130/STAT3 signaling pathway. Chem Biol Interact 2022;352:109779.
• Caner V, Cetin GO, Hacioglu S, Baris IC, Tepeli E, Sen Turk N, et al. The miRNA content of circulating exosomes in DLBCL patients and in vitro influence of DLBCL-derived exosomes on miRNA expression of healthy B cells from peripheral blood. Cancer Biomark 2021;32(4):519-529.
• Lopez-Santillan M, Larrabeiti-Etxebarria A, Arzuaga-Mendez J, Lopez-Lopez E, Garcia-Orad A. Circulating miRNAs as biomarkers in diffuse large B-cell lymphoma: a systematic review. Oncotarget 2018;9(32):22850-22861.
• Shedden K, Xie XT, Chandaroy P, Chang YT. Rosania G.R. Expulsion of small molecules in vesicles shed by cancer cells: Association with gene expression and chemosensitivity profiles. Cancer Res 2003;63:4331–4337.
• Aung T, Chapuy B, Vogel D, Wenzel D, Oppermann M, Lahmann M, et al. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3. Proc Natl Acad Sci U S A. 2011;108(37):15336-41.
• Oksvold MP, Kullmann A, Forfang L, Kierulf B, Li M, Brech A, et al. Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells. Clin Ther 2014;36(6): 847-862.
• Beck A, Goetsch L, Dumontet C, & Corvaïa N. Strategies and challenges for the next generation of antibody‐drug conjugates. Nature Reviews Drug Discovery 2017;16(5):315–337. Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trneny M, Sharman JP, et al. Polatuzumab Vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med 2022;386(4):351–63.
• Prakash R, Subbiah V, Iyer SP. Evolving Landscape of Antibody Drug Conjugates in Lymphoma. Cancer J 2022;28(6):479-487.
• Hansen HP, Trad A, Dams M, Zigrino P, Moss M, Tator M, et al. CD30 on extracellular vesicles from malignant Hodgkin cells supports damaging of CD30 ligand-expressing bystander cells with Brentuximab-Vedotin, in vitro. Oncotarget 2016;7(21):30523-35.
• Barıs IC, Hacıoglu S, Turk NS, Cetın GO, Zencır S, Bagcı G, et al. Expression and DNA methylation profiles of EZH2-target genes in plasma exosomes and matched primary tumor tissues of the patients with diffuse large B-cell lymphoma. Clin Transl Oncol 2021;23(6):1152-1166.
• Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantstohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7(1):1535750.
• Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, et al. Phase 2 study of the bispecific T-cell engager (bite) antibody Blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood 2016;127(11):1410–1416.
• Chen Z, You L, Wang L, Huang X, Liu H, Wei JY, Zhu L, Qian W. Dual effect of DLBCL-derived EXOs in lymphoma to improve DC vaccine efficacy in vitro while favor tumorgenesis in vivo. J Exp Clin Cancer Res 2018;37(1):190.
• Manches O, Lui G, Chaperot L, Gressin R, Molens JP, Jacob MC, et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 2003;101:949–954.
• Hu S, Xu-Monette ZY, Balasubramanyam A, Manyam GC, Visco C, Tzankov A, et al. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene. Blood 2013;121(14):2715-24.
• Hao X, Wei X, Huang F, Wei Y, Zeng, H, Xu, et al. The expression of CD30 based on immunohistochemistry predicts inferior outcome in patients with diffuse large B-cell lymphoma. PLoS One 2015;10(5):e0126615.
• Svoboda J, Bair SM, Landsburg DJ, Dwivedy NS, Nagle SJ, Barta SK, et al. Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas. Haematologica 2021;106(6):1705-1713.
• Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, et al. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma 2017;58(7):1607-1616.
• Kim SJ, Yoon DH, Kim JS, Kang HJ, Lee HW, Eom HS, et al. Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30-Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial. Cancer Res Treat 2020;52(2):374-387.
• Hansen HP, Paes Leme AF, Hallek M. Role of ADAM10 as a CD30 Sheddase in Classical Hodgkin Lymphoma. Front Immunol 2020;11:398.
• Lobastova L, Lettau M, Babatz F, de Oliveira TD, Nguyen PH, Pauletti BA, et al. CD30-Positive Extracellular Vesicles Enable the Targeting of CD30-Negative DLBCL Cells by the CD30 Antibody-Drug Conjugate Brentuximab Vedotin. Front Cell Dev Biol 2021;9:698503.
• Sehn LH, Matasar MJ, Flowers, CR, Kamdar M, McMillan AK, Hertzberg M, et al. Polatuzumab vedotin plus bendamustine with rituximab in relapsed/refractory diffuse large B‐cell lymphoma: updated results of a phase Ib/II randomized study. Blood 2019;134:4081.
• Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2020;38:155-65.
• Pfeifer M, Zheng B, Erdmann T, Koeppen H, McCord R, Grau M et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015;29(7):1578–1586.
• Barok M, Puhka M, Yazdi N, Joensuu H. Extracellular vesicles as modifiers of antibody-drug conjugate efficacy. J Extracell Vesicles 10(4):e12070.
• Swerdlow SH, Campo E & Harris NL. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. France: Lyon; 2008.
• Salles G, de Jong D, Xie W, Rosenwald A, Chhanabhai M, Gaulard P, et al. Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma:a study from the Lunenburg Lymphoma Biomarker Consortium Blood 2011;117(26):7070-8.