Citations 1
Malignant B-cell States Orchestrate Spatially Organized Immune Ecosystems in B-cell Lymphomas
Mondello, Patrizia , Sadekova, Alisa , fede, ksenia, Dasari, Surendra , Au, Wesley , Kriukov, Kirill , Meerson, Mark, Novak, Joseph, Yang, Zhi-Zhang , Gysbers, Brianna J. , Villasboas, Jose, Wiebe, Daniil S. , Shvyrkova, Anastasiia, Margaryan, Sargis, Nesmelov, Alexander, Sarachakov, Aleksander, Petrosyants, Arman, Bagaev, Alexander , Novak, Anne J. , Casulo, Carla, Hsi, Eric, Fowler, Nathan, King, Rebecca, Singh, Harinder, Armand, Philippe, Pasqualucci, Laura, Ansell, Stephen M. , Binder, Moritz , Yang, Zhi-Zhang , Gysbers, Brianna J , Postovalova, Ekaterina , Wiebe, Daniil , Kotlov, Nikita , Wang, Yucai , Novak, Anne J , Habermann, Thomas , Maurer, Matthew , Cerhan, James R , Shlomchik, Mark , Ansell, Stephen M , Mondello, Patrizia , Dasari, Surendra , Au, Wesley, Binder, Moritz , Meerson, Mark , Novak, Joseph P. , Villasboas, José C. , Guzman, Emmanuel Contreras , Nesmelov, Alexander, Wang, Yucai , Habermann, Thomas M. , Hsi, Eric D. , Maurer, Matthew J. , Cerhan, James R. , Singh, Harinder, Armand, P., Pasqualucci, Laura , Burack, Richard
No container title available | August 3, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Germinal center (GC)-derived lymphomas arise within a specialized immune ecosystem, yet whether malignant cells direct its remodeling remains unclear. Integrating genomic, transcriptomic, spatial, and functional analyses across follicular lymphoma and diffuse large B-cell lymphoma, we define a developmental framework linking malignant B-cell differentiation state to tumor microenvironment (TME) organization. Rather than segregating by histology, lymphomas align along a shared differentiation continuum in which proliferative dark zone (DZ) states associate with immune-depleted TMEs, whereas post-GC/memory B-cell (MBC) states drive inflamed but immunosuppressed TMEs. Spatial profiling reveals collapse of GC architecture and emergence of suppressive myeloid niches along this trajectory. Single-cell lineage reconstruction uncovers a DZ-to-MBC developmental axis underlying lymphoma evolution. Genetic reprogramming in vivo demonstrates that malignant differentiation state is sufficient to instruct TME remodeling. Collectively, these findings establish malignant differentiation state as a causal determinant of immune architecture across GC-derived lymphomas and identify lineage-directed immune reprogramming as a potential therapeutic strategy.