Project description:
CAR-T cell therapy has revolutionized the treatment of patients with B cell lymphomas. However, only about half of these patients achieve durable benefit from this therapy. Using state-of-the-art cell biological techniques, the team identified so-called CSF1R-positive myeloid-monocytic cells (LAMM cells) in patient tissue that are associated with a non-durable response to CAR-T cell therapy. Further investigations showed that LAMM cells impair CAR-T cell function and can thus contribute to therapy failure. In a preclinical mouse model, targeted blockade of LAMM cells with a CSF1R inhibitor enhanced CAR-T cell efficacy. The goal is to advance this promising combination therapy of CAR-T cells and CSF1R inhibition in a clinical study involving patients with B-cell lymphomas.
Publication:
Stahl D*, Gödel P*, Balke-Want H*, Gholamipoorfard R, Segbers P, Tetenborg L, Koker M, Dörr J, Gregor L, Bachurski D, Rose F, Simon AG, Good Z, Jakob J, Häupl B, Nill M, Flümann R, Riet T, Lange D, Blakemore SJ, Baurmann H, Voltin CA, Potter N, Schlözer L, Freihammer M, Wagener-Ryczek S, Iuga AI, Heger JM, Ludwig H, Schleifenbaum JK, Propp J, Bröckelmann PJ, Jachimowicz RD, 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 SJ, Büttner R, Oellerich T, Hallek M, Kobold S, Chmielewski M, Reinhardt HC, Mackall C, Abedpour N, Borchmann P, Ullrich RT. CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma. Cancer Cell. 2025 Aug 11;43(8):1476-1494.e10. *contributed equally
Paper: https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00222-3
Submitting the Paper of the Month:
Else Kröner-Fresenius-Stiftung is using the series “Paper of the Month” to report in an exemplary and hot-off-the-press style on the outstanding work being done by the scientists it supports. We regularly present publications which have recently appeared in especially renowned journals, have emerged from foundation funding and been given appropriate acknowledgment. This is done in the respective categories “Original Paper” and “Review”. In the case of each of these publications, the first author and/or senior author are being funded by the foundation.
We invite all project managers, fellowship recipients and members of graduate study programs to send their work in accordance with the stated criteria as proposal for Paper of the Month to Ms. Anne Asschenfeldt (a.asschenfeldt@ekfs.de).
More Paper of the Month can be found here.
