ORCID: https://orcid.org/0000-0002-2898-4182; Grünmeier, Ruth ORCID: https://orcid.org/0000-0002-9044-3600; Hoffmann, Gordon Victor ORCID: https://orcid.org/0009-0007-3167-2124; Nandi, Sayantan; Kavaka, Vladyslav ORCID: https://orcid.org/0009-0004-5837-3384; Müller, Philipp Jie; Jobst, Jakob; Öner, Arman ORCID: https://orcid.org/0000-0003-2754-5417; Kaiser, Rainer ORCID: https://orcid.org/0000-0003-1750-3395; Gärtig, Jan; Piseddu, Ignazio ORCID: https://orcid.org/0000-0001-8331-9778; Frenz-Wießner, Stephanie ORCID: https://orcid.org/0000-0001-8862-3752; Fairley, Savannah D. ORCID: https://orcid.org/0009-0001-8310-2074; Schulz, Heiko; Igl, Veronika ORCID: https://orcid.org/0000-0003-4618-2383; Janert, Thomas Alexander ORCID: https://orcid.org/0009-0007-2466-7650; Di Fina, Lea; Mulkers, Maité ORCID: https://orcid.org/0009-0003-4402-2682; Thomas, Moritz ORCID: https://orcid.org/0000-0002-8422-2414; Briukhovetska, Daria ORCID: https://orcid.org/0000-0002-2073-2335; Simnica, Donjetë ORCID: https://orcid.org/0000-0003-2286-1381; Carlini, Emanuele; Tsiverioti, Christina Angeliki ORCID: https://orcid.org/0009-0008-4055-1196; Trefny, Marcel P. ORCID: https://orcid.org/0000-0001-6755-7899; Lorenzini, Theo ORCID: https://orcid.org/0000-0003-3377-032X; Märkl, Florian ORCID: https://orcid.org/0000-0003-4285-0380; Mesquita, Pedro ORCID: https://orcid.org/0009-0007-4285-9269; Brabenec, Ruben ORCID: https://orcid.org/0000-0002-8820-220X; Strzalkowski, Thaddäus ORCID: https://orcid.org/0000-0002-7191-0410; Stock, Sophia ORCID: https://orcid.org/0000-0002-5072-5013; Michaelides, Stefanos ORCID: https://orcid.org/0000-0002-9001-0207; Hellmuth, Johannes C. ORCID: https://orcid.org/0000-0001-8409-3037; Thelen, Martin ORCID: https://orcid.org/0000-0002-2785-9726; Reinke, Sarah ORCID: https://orcid.org/0000-0001-9729-4030; Klapper, Wolfram; Gelebart, Pascal Francois ORCID: https://orcid.org/0000-0003-2434-8987; Nicolai, Leo ORCID: https://orcid.org/0000-0003-0776-5885; Marr, Carsten; Beltrán, Eduardo ORCID: https://orcid.org/0000-0002-7266-4098; Megens, Remco T. A. ORCID: https://orcid.org/0000-0001-9871-6696; Klein, Christoph; Baran-Marszak, Fanny; Rosenwald, Andreas; Bergwelt-Baildon, Michael von ORCID: https://orcid.org/0000-0002-1952-052X; Bröckelmann, Paul J. ORCID: https://orcid.org/0000-0001-9662-9900; Endres, Stefan ORCID: https://orcid.org/0000-0002-4703-537X und Kobold, Sebastian ORCID: https://orcid.org/0000-0002-5612-4673
(2025):
Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.
In: Blood, Vol. 145, No. 14: pp. 1536-1552
[PDF, 6MB]
Abstract
The success of targeted therapies for hematological malignancies has heralded their potential as both salvage treatment and early treatment lines, reducing the need for high-dose, intensive, and often toxic chemotherapeutic regimens. For young patients with classic Hodgkin lymphoma (cHL), immunotherapies provide the possibility to lessen long-term, treatment-related toxicities. However, suitable therapeutic targets are lacking. By integrating single-cell dissection of the tumor landscape and an in-depth, single-cell–based off-tumor antigen prediction, we identify CD86 as a promising therapeutic target in cHL. CD86 is highly expressed on Hodgkin and Reed-Sternberg cancer cells and cHL-specific tumor-associated macrophages. We reveal CD86–CTLA-4 as a key suppressive pathway in cHL, driving T-cell exhaustion. Cellular therapies targeting CD86 had extraordinary efficacy in vitro and in vivo and were safe in immunocompetent mouse models without compromising bacterial host defense in sepsis models. Our results prove the potential value of anti-CD86 immunotherapies for treating cHL.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine > Institute of Pathology Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic I (Cardiology) Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic III (Oncology) Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic IV (Endocrinology, nephrology, other sections) Medicine > Medical Center of the University of Munich > Pediatric Clinic and Outpatient Clinic in the Dr. von Hauner Children‘s Hospital |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-125956-5 |
| ISSN: | 0006-4971 |
| Language: | English |
| Item ID: | 125956 |
| Date Deposited: | 13. May 2025 13:46 |
| Last Modified: | 13. May 2025 13:46 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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