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Stahl, D.* ; Gödel, P.* ; Balke-Want, H.* ; Gholamipoorfard, R.* ; Segbers, P.* ; Tetenborg, L.* ; Koker, M.* ; Dörr, J.* ; Gregor, L.* ; Bachurski, D.* ; Rose, F.* ; Simon, A.G.* ; Good, Z.* ; Jakob, J.* ; Häupl, B.* ; Nill, M.* ; Flümann, R.* ; Riet, T.* ; Lange, D.* ; Blakemore, S.J.* ; Baurmann, H.* ; Voltin, C.A.* ; Potter, N.* ; Schlözer, L.* ; Freihammer, M.* ; Wagener-Ryczek, S.* ; Iuga, A.I.* ; Heger, J.M.* ; Ludwig, H.* ; Schleifenbaum, J.K.* ; Propp, J.* ; Bröckelmann, P.J.* ; Jachimowicz, R.D.* ; Knittel, G.* ; Borchmann, S.* ; Merkelbach-Bruse, S.* ; Pallasch, C.P.* ; Peifer, M.* ; Rybniker, J.* ; Quaas, A.* ; Nitz, M.* ; Brägelmann, J.* ; Müller, W.* ; Persigehl, T.* ; Bozek, K.* ; Theobald, S.J.* ; Büttner, R.* ; Oellerich, T.* ; Hallek, M.* ; Kobold, S. ; Chmielewski, M.* ; Reinhardt, H.C.* ; Mackall, C.* ; Abedpour, N.* ; Borchmann, P.* ; Ullrich, R.T.*

CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma.

Cancer Cell 43, 1476-1494.e10 (2025)
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Despite the improvement, approximately 60% of patients with relapsed or refractory (r/r) aggressive B cell lymphoma (B-NHL) do not achieve durable benefit from CAR-T cell therapy. To elucidate factors associated with CAR-T therapy resistance, we conducted high-dimensional analyses of pre- and post-CAR-T cell specimens. In patients with non-durable response, we identified a prognostically relevant lymphoma-associated myeloid-monocytic (LAMM) gene signature. In-depth profiling revealed a distinct CSF1R+CD14+CD68+ LAMM cell population in both human and murine B-NHL that inhibits CAR-T cell function and correlates with poor outcome. Cell-cell inference analysis uncovered that LAMM cells impair CAR-T cell function through a direct LAMM-T cell interaction via the PGE2-EP2/EP4 axis. In an autochthonous lymphoma mouse model, combined anti-CD19 CAR-T cell therapy with CSF1R blockade exhibited synergistic effects and improved survival. These findings provide strong rationale for combining anti-CD19 CAR-T cells with CSF1R inhibitors in treating r/r aggressive B-NHL patients.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Car-t Cell ; Csf1r ; Aggressive B-nhl ; Lymphoma Tumor Microenvironment ; Myeloid Cells; Tumor-associated Macrophages; Suppressor-cells; Follow-up; Rna-seq; Expression; Tissue; Overexpression; Monocytes; Cancer
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Journal Cancer Cell
Quellenangaben Volume: 43, Issue: 8, Pages: 1476-1494.e10 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-522100-001
Grants Deutsche Krebshilfe (German Cancer Aid)
Else Kroner-Fresenius Foundation (EKFS)
Ministry of Culture and Science of the State of Northrhine Westphalia (Germany) as part of the Cancer Center Cologne Essen
CANTAR network through the program "Netzwerke 2021"
Koln Fortune grant
Deutsche Forschungsgemeinschaft (German Research Foundation)
Faculty of Medicine Cologne
ERA-PerMed program (HighRisk-HighGain consortium)
Bavarian Cancer Research Center (BZKF, TANGO)
Dr.-Rurainski Foundation
Fritz Bender Foundation
Deutsche Jose Carreras Leukamie-Stiftung
Hector Foundation
Bavarian Research Foundation (BAYCELLATOR)
Bruno and Helene Joster Foundation
Monika Kutzner Foundation for Cancer Research
German Center for Infection Research (DZIF, TTU-TB grants)
German Federal Ministry of Education and Research (BMBF)
European Research Council
Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer (Horizon 2020 programme of the European Union)
European Union Innovative Medicines Initiative 2 Joint Undertaking program
CMMC
Wilhelm Sander-Stiftung
Go-Bio-Initiative
Imhoff Stiftung
Bavarian Ministry for Economical Affairs
Koln Fortune Program
Bundesministerium fur Bildung und Forschung
Jubilaumsstiftung 1988 (University of Cologne)
DOI 10.1016/j.ccell.2025.05.013
WOS ID 001604737800001
Scopus ID 105008030519
PubMed ID 40513575
Erfassungsdatum 2025-07-09
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