TY - JOUR A1 - Munawar, Umair A1 - Zhou, Xiang A1 - Prommersberger, Sabrina A1 - Nerreter, Silvia A1 - Vogt, Cornelia A1 - Steinhardt, Maximilian J. A1 - Truger, Marietta A1 - Mersi, Julia A1 - Teufel, Eva A1 - Han, Seungbin A1 - Haertle, Larissa A1 - Banholzer, Nicole A1 - Eiring, Patrick A1 - Danhof, Sophia A1 - Navarro-Aguadero, Miguel Angel A1 - Fernandez-Martin, Adrian A1 - Ortiz-Ruiz, Alejandra A1 - Barrio, Santiago A1 - Gallardo, Miguel A1 - Valeri, Antonio A1 - Castellano, Eva A1 - Raab, Peter A1 - Rudert, Maximilian A1 - Haferlach, Claudia A1 - Sauer, Markus A1 - Hudecek, Michael A1 - Martinez-Lopez, J. A1 - Waldschmidt, Johannes A1 - Einsele, Hermann A1 - Rasche, Leo A1 - Kortüm, K. Martin T1 - Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma JF - Communications Biology N2 - The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM. KW - immunotherapy KW - translational research Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357609 VL - 6 ER -