Lymphoma organoid models for evaluating and targeting tumor immune microenvironment

Abstract

Lymphoma organoid models are very powerful new tools. They excel at recapitulating certain patient-specific features—for example, the interplay of a patient’s T cells with their tumor B cells—and thereby offer unprecedented opportunities for in vitro immunotherapy trials on patient tissue. However, current models still fall short of recreating the full complexity of the lymphoma microenvironment, including the circulatory system, a complete immune repertoire, and long-term tumor–immune dynamics. Ongoing improvements aim to extend immune cell longevity, include additional immune and stromal components, and standardize protocols to reduce technical variability. As these challenges are addressed, lymphoma organoids are expected to become increasingly reliable and predictive. Already, their success in modeling patient responses is encouraging, and careful validation is needed. Ultimately, the integration of organoid assays into preclinical and clinical workflows will require a balanced understanding of their limitations—using organoids as complementary to clinical judgment and genomic biomarkers, rather than infallible stand-alone predictors. With continued refinement, lymphoma organoid co-cultures hold great promise to bridge the gap between laboratory testing and real-world patient outcomes, accelerating the development of truly personalized cancer therapies.