@article{MunawarZhouPrommersbergeretal.2023, author = {Munawar, Umair and Zhou, Xiang and Prommersberger, Sabrina and Nerreter, Silvia and Vogt, Cornelia and Steinhardt, Maximilian J. and Truger, Marietta and Mersi, Julia and Teufel, Eva and Han, Seungbin and Haertle, Larissa and Banholzer, Nicole and Eiring, Patrick and Danhof, Sophia and Navarro-Aguadero, Miguel Angel and Fernandez-Martin, Adrian and Ortiz-Ruiz, Alejandra and Barrio, Santiago and Gallardo, Miguel and Valeri, Antonio and Castellano, Eva and Raab, Peter and Rudert, Maximilian and Haferlach, Claudia and Sauer, Markus and Hudecek, Michael and Martinez-Lopez, J. and Waldschmidt, Johannes and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin}, title = {Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma}, series = {Communications Biology}, volume = {6}, journal = {Communications Biology}, doi = {10.1038/s42003-023-05683-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357609}, year = {2023}, abstract = {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.}, language = {en} }