Plasticity and state transitions in mature lymphoid cells and malignancies: Drivers of fitness, evolution, and therapeutic resistance

Cellular plasticity is a fundamental property of the immune system, enabling lymphoid cells to dynamically adapt their identity and function in response to environmental cues. In secondary lymphoid organs, cells undergo iterative cycles of activation, selection, and differentiation, supported by various extrinsic microenvironment signals and tightly regulated intrinsic 3D chromatin and epigenetic programs. Increasing evidence indicates that malignant lymphoid cells hijack these physiological programs, adopting dynamic and reversible cell states that fuel tumour heterogeneity. Beyond static classifications, lymphoid malignancies are now recognized as ecosystems of interconverting cellular states. However, current frameworks remain fragmented, often separating normal differentiation, tumour biology, and therapeutic response. A unified understanding of how plasticity operates along a continuum between normal GC B cell states, plastic intermediates, transdifferentiation and malignant reprogramming remains lacking.This Research Topic aims to establish a unifying framework in which cellular plasticity is viewed as a central driver of fitness, clonal evolution, and therapeutic resistance in lymphoid cells and malignancies. Rather than describing plasticity as a passive feature, we seek to understand how dynamic state transitions actively shape adaptive immunity, tumor adaptability, repopulation capacity, and treatment response. Recent advances—including single-cell multi-omics, lineage tracing, and 3D genome mapping—have revealed the extent of cellular heterogeneity and the regulatory circuits that enable state transitions. Yet, the functional consequences of these transitions and their integration with microenvironmental signals remain insufficiently explored.This collection will bring together studies that dissect the molecular and cellular mechanisms governing plasticity, with particular emphasis on epigenetic and chromatin-based regulation, and their role in disease progression and resistance. Ultimately, the goal is to identify actionable vulnerabilities within plastic states and to inform strategies that limit tumor evolution or reprogram malignant cell fates.We welcome contributions addressing shared clonal origin and cellular plasticity across B, T, and NK cell malignancies, integrating insights from normal lymphoid biology and cancer. Topics of interest include, but are not limited to, mechanisms of cell-state transitions; the role of epigenetic regulation and 3D chromatin architecture; microenvironmental cues; Immune evasion; clonal evolution and fitness landscapes; and the contribution of plasticity to therapy resistance and relapse. We invite a range of article types, including Original Research, Reviews, Mini-Reviews, and Perspectives. Submissions employing cutting-edge approaches such as single-cell and spatial omics, lineage tracing, and functional perturbation systems are especially encouraged. Work that provides conceptual advances or translational insights into targeting plasticity will be prioritized. Topic editors: Laurianne Scourzic, Tim Pieters Source: https://www.frontiersin.org/research-topics/80830/plasticity-and-state-transitions-in-mature-lymphoid-cells-and-malignancies-drivers-of-fitness-evolution-and-therapeutic-resistance