Diffuse large B-cell lymphoma is the most common malignant disease of the lymphatic system, with an incidence of around 7 in 100.000 citizens in Germany. It is a disease originating from mature B-cells, which can be classified using morphologic, immunologic and molecular criteria. Despite constant progress in therapy and a curative treatment strategy, with the R-CHOP-protocol being the first-line therapy for most patients, complete remission can be achieved in only around 60 percent of patients. The prognosis for patients in relapse or refractory disease (r/r) is very poor with a median survival of 6.3 months after the start of salvage therapy. Therefore, the need for new treatment options and strategies to enhance the effect of the existing therapies remains great. One very promising and already established strategy is CAR T cell therapy, from which patients both in early and late relapse have been proven to benefit from.

CAR T cells are a therapy approach in which T cells, normally obtained from the patient by leukapheresis, are genetically modified in order to express a receptor targeted against selected antigens on the surface of the malignant cells. Despite their great success in patients with malignant diseases, several resistance mechanisms have been described, limiting the effectiveness of this treatment strategy. One relevant resistance mechanism - the obstruction of CAR T cell proliferation and penetration into the lymphoma tissue due to an immunosuppressive tumour microenvironment (TME) - promises to offer novel possibilities to enhance CAR T cell therapy success.

We could recently show that an immunosuppressive lymphoma-associated myelo-monocytic (LAMM) cells limit the efficacy of CAR T cell therapy by directly inhibiting CAR T cell function. We found that these LAMM cells are highly positive for SYK indicating a relevant role of SYK signalling for LAMM cell function. Based on these findings, we now aim to identify the possible effect of SYK-Inhibition on the success of CAR T cell therapy and the underlying mechanisms responsible for this.

https://innere1.uk-koeln.de/forschung/arbeitsgruppen-labore/krebstherapie-und-molekulare-bildgebung/