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@ARTICLE{Gottschlich:300241,
author = {A. Gottschlich$^*$ and R. Grünmeier and G. V. Hoffmann and
S. Nandi and V. Kavaka and P. J. Müller and J. Jobst and A.
Oner and R. Kaiser and J. Gärtig and I. Piseddu and S.
Frenz-Wiessner and S. D. Fairley and H. Schulz and V. Igl
and T. A. Janert and L. Di Fina and M. Mulkers and M. Thomas
and D. Briukhovetska and D. Simnica and E. Carlini and C. A.
Tsiverioti and M. P. Trefny and T. Lorenzini and F. Märkl
and P. Mesquita and R. Brabenec and T. Strzalkowski and S.
Stock$^*$ and S. Michaelides and J. Hellmuth and M. Thelen
and S. Reinke and W. Klapper and P. F. Gelebart and L.
Nicolai and C. Marr and E. Beltrán and R. T. A. Megens and
C. Klein and F. Baran-Marszak and A. Rosenwald and M. von
Bergwelt-Baildon$^*$ and P. J. Bröckelmann and S.
Endres$^*$ and S. Kobold$^*$},
title = {{D}issection of single-cell landscapes for the development
of chimeric antigen receptor {T} cells in {H}odgkin
lymphoma.},
journal = {Blood},
volume = {145},
number = {14},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2025-00702},
pages = {1536-1552},
year = {2025},
note = {2025 Apr 3;145(14):1536-1552},
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.},
keywords = {Hodgkin Disease: therapy / Hodgkin Disease: immunology /
Hodgkin Disease: pathology / Humans / Animals / Mice /
Receptors, Chimeric Antigen: immunology / B7-2 Antigen:
immunology / T-Lymphocytes: immunology / Immunotherapy,
Adoptive: methods / Single-Cell Analysis / Female / Cell
Line, Tumor / Receptors, Chimeric Antigen (NLM Chemicals) /
B7-2 Antigen (NLM Chemicals)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40178843},
doi = {10.1182/blood.2023022197},
url = {https://inrepo02.dkfz.de/record/300241},
}