Image 2_Spatial immune ecosystems and therapy resistance in large B-cell lymphoma: from single-cell multi-omics to immunotherapy-matched validation.tiff

Although molecular classification has refined the understanding of lymphoma biology, relapse after chemoimmunotherapy, chimeric antigen receptor (CAR) T-cell therapy, CD20×CD3 bispecific antibodies, antibody-drug conjugates (ADCs), and immune-combination strategies cannot be explained by genetics or target-antigen expression alone.

Single-cell and spatial multi-omics now allow lymphoma to be interpreted as a spatial immune ecosystem composed of malignant B-cell states, exhausted or regulatory T-cell programs, myeloid suppressive hubs, stromal and vascular compartmentalization, metabolic gradients, and local communication networks. This Review synthesizes recent DLBCL and large B-cell lymphoma ecosystem studies from a cancer-immunology perspective, emphasizing how spatial immune organization may influence effector access, antigen engagement, macrophage-mediated suppression, antibody exposure, and treatment-associated spatial change.