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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, DOI: 10.1016/j.ccell.2025.05.013 (2025)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Car-t Cell ; Csf1r ; Aggressive B-nhl ; Lymphoma Tumor Microenvironment ; Myeloid Cells
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Verlag Cell Press
Verlagsort Cambridge, Mass.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Unit for Clinical Pharmacology (KKG-EKLiP)