TY  - JOUR
AU  - Gottschlich, Adrian
AU  - Grünmeier, Ruth
AU  - Hoffmann, Gordon Victor
AU  - Nandi, Sayantan
AU  - Kavaka, Vladyslav
AU  - Müller, Philipp Jie
AU  - Jobst, Jakob
AU  - Oner, Arman
AU  - Kaiser, Rainer
AU  - Gärtig, Jan
AU  - Piseddu, Ignazio
AU  - Frenz-Wiessner, Stephanie
AU  - Fairley, Savannah D
AU  - Schulz, Heiko
AU  - Igl, Veronika
AU  - Janert, Thomas Alexander
AU  - Di Fina, Lea
AU  - Mulkers, Maité
AU  - Thomas, Moritz
AU  - Briukhovetska, Daria
AU  - Simnica, Donjetë
AU  - Carlini, Emanuele
AU  - Tsiverioti, Christina Angeliki
AU  - Trefny, Marcel P
AU  - Lorenzini, Theo
AU  - Märkl, Florian
AU  - Mesquita, Pedro
AU  - Brabenec, Ruben
AU  - Strzalkowski, Thaddäus
AU  - Stock, Sophia
AU  - Michaelides, Stefanos
AU  - Hellmuth, Johannes
AU  - Thelen, Martin
AU  - Reinke, Sarah
AU  - Klapper, Wolfram
AU  - Gelebart, Pascal Francois
AU  - Nicolai, Leo
AU  - Marr, Carsten
AU  - Beltrán, Eduardo
AU  - Megens, Remco T A
AU  - Klein, Christoph
AU  - Baran-Marszak, Fanny
AU  - Rosenwald, Andreas
AU  - von Bergwelt-Baildon, Michael
AU  - Bröckelmann, Paul J
AU  - Endres, Stefan
AU  - Kobold, Sebastian
TI  - Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.
JO  - Blood
VL  - 145
IS  - 14
SN  - 0006-4971
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2025-00702
SP  - 1536-1552
PY  - 2025
N1  - 2025 Apr 3;145(14):1536-1552
AB  - 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.
KW  - Hodgkin Disease: therapy
KW  - Hodgkin Disease: immunology
KW  - Hodgkin Disease: pathology
KW  - Humans
KW  - Animals
KW  - Mice
KW  - Receptors, Chimeric Antigen: immunology
KW  - B7-2 Antigen: immunology
KW  - T-Lymphocytes: immunology
KW  - Immunotherapy, Adoptive: methods
KW  - Single-Cell Analysis
KW  - Female
KW  - Cell Line, Tumor
KW  - Receptors, Chimeric Antigen (NLM Chemicals)
KW  - B7-2 Antigen (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40178843
DO  - DOI:10.1182/blood.2023022197
UR  - https://inrepo02.dkfz.de/record/300241
ER  -