Journal Article

DKFZ-2025-01230

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma.

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.DKFZ* ; 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. ; Peifer, M. ; Rybniker, J. ; Quaas, A. ; Nitz, M. ; Brägelmann, J. ; Müller, W. ; Persigehl, T. ; Bozek, K. ; Theobald, S. J. ; Büttner, R. ; Oellerich, T.DKFZ* ; Hallek, M. ; Kobold, S.DKFZ* ; Chmielewski, M. ; Reinhardt, H. C.DKFZ* ; Mackall, C. ; Abedpour, N. ; Borchmann, P. ; Ullrich, R. T.

2025
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccell.2025.05.013

Abstract: 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.

Keyword(s): CAR-T cell ; CSF1R ; aggressive B-NHL ; lymphoma tumor microenvironment ; myeloid cells

Note: 2025 Aug 11;43(8):1476-1494.e10

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Frankfurt (FM01)
2. DKTK Koordinierungsstelle München (MU01)
3. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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