Most cancers originate from alterations in stem or progenitor cells, from which normal tissues develop. These cells are responsible for the development and continuous regeneration of tissues and have the capacity to give rise to the multiple cell types that make up the human body. This ability to generate different cell types is called plasticity. Normally, cells lose this property when they cease to be stem or progenitor cells.

Lymphomas develop in the lymph nodes from mature B lymphocytes, which is surprising since mature cells typically lack the plasticity considered necessary for tumour formation. However, these immune cells exhibit peculiar characteristics, possessing a great capacity for division and transition between very different functional states.

A recent study, the result of a collaboration between Dr Effie Apostolou of Weill Cornell Medicine (USA) and Dr Ari Melnick, director of the Josep Carreras Institute, has just demonstrated that the activation of mature B lymphocytes induces a stem cell-like state. “We know that these B lymphocytes are mature and fully differentiated, but they still exhibit characteristics reminiscent of stem cells,” explains Dr Apostolou. “This goes against the central dogma that cells lose their plasticity and regenerative capacity as they mature.”

The study, recently published in the journal Nature Cell Biology, describes how contact with T lymphocytes triggers epigenetic changes within B lymphocytes that dilute their mature cell identity, allowing them to rapidly change function and state. The researchers hypothesize that certain mutations in B lymphocytes could exploit this natural plasticity to initiate tumour development.

“All the characteristics we have identified in this process of acquired plasticity appear to be enhanced in many patients with lymphomas and correlate with a worse prognosis,” says Dr Apostolou. “We believe that this natural process, which is finely regulated during immune system activation, could be hijacked by specific mutations to promote the development of lymphoma.”

“Tumour plasticity is what allows cancers to evade current treatments,” adds Dr Melnick, who points out that “in this work, we have identified a treatment that blocks the plasticity of these cells, which could become a new form of ‘antiplasticity’ therapy, capable of making immunotherapies and other treatments more effective.” The research team is currently evaluating whether these antiplasticity drugs can be translated into clinical practice.

This research, supported by the most advanced technologies for genetic analysis at the single-cell level, has made it possible to identify key elements of lymphoma biology that facilitate its development. This knowledge will allow for improved prediction of disease progression and optimize the selection of personalized therapies for each patient.

Reference Article: Scourzic, L., Izzo, F., Teater, M. et al. T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response. Nat Cell Biol (2025). https://doi.org/10.1038/s41556-025-01833-4