B cell non-Hodgkin lymphomas (B-NHL), particularly diffuse large B-cell lymphoma (DLBCL), are the most common aggressive lymphomas. While many patients can be cured with first-line immunochemotherapy, a substantial proportion develop relapsed or refractory (R/R) disease. For these patients, CD19-directed chimeric antigen receptor (CAR)-T cell therapy has substantially improved treatment options. Despite the therapeutic potential of CAR-T cell therapy, approximately 60% of patients with relapsed or refractory (R/R) aggressive B cell lymphoma (B-NHL) do not achieve a durable response. Increasing evidence suggests that the lymphoma microenvironment (LME), including immunosuppressive myeloid and lymphoid cell populations, plays an important role in CAR-T cell dysfunction and treatment resistance. Understanding and therapeutically modulating the LME is therefore crucial to improve CAR-T cell efficacy.

My project will investigate whether activation of the stimulator of interferon genes (STING) pathway can modulate the LME towards a more immune-supportive state and thereby enhance CAR-T cell responses. STING, encoded by TMEM173, is a central component of the innate immune system and promotes type I interferon and inflammatory signaling upon activation of the cGAS-STING pathway. By analyzing how STING activation affects the cellular composition and functional state of the LME, we aim to address key barriers to therapeutic efficacy of CAR-T cell therapy by using a possible co-treatment with STING agonists.

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