Weill Cornell Study Reframes Hodgkin Lymphoma as a Malignancy of Arrested Immune Cell Development

Weill Cornell researchers find Hodgkin lymphoma cells are B cells trapped during plasma cell transition, revealing new targets for adolescent cancer diagnostics.

By: AXL Media

Published: Apr 25, 2026, 8:51 AM EDT

Source: Information for this report was sourced from EurekAlert!

A Developmental Identity Crisis in the Immune System

New evidence from Weill Cornell Medicine has revealed that Hodgkin lymphoma is essentially a cancer of failed maturation rather than just rapid cell division. Researchers demonstrated that the hallmark Reed-Sternberg cells are actually B cells that have abandoned their original features but failed to complete the transition into functional, antibody producing plasma cells. This biological stall leaves the cells in a permanent state of developmental limbo. Dr. Ethel Cesarman, a professor of pathology and laboratory medicine, noted that while these cells were on the pathway to becoming plasma cells, the process was aborted due to an inability to produce immunoglobulins.

Comparative Analysis of Gene Expression Profiles

To pinpoint the origin of these malignant cells, the research team conducted an extensive gene expression analysis on 18 primary tumors and four specialized cell lines. They compared Hodgkin lymphoma against primary mediastinal B cell lymphoma, a similar cancer found in the same thoracic location. The findings showed that Hodgkin lymphoma cells share a closer genetic resemblance to multiple myeloma, a plasma cell cancer, than to other lymphomas. Dr. Isabella Kong, a postdoctoral associate, explained that the cells downregulate B cell proteins while upregulating plasma cell proteins, though they never achieve the state of a fully functioning immune cell.

The Survival Mechanism of Internal Stress Responses

Because these cells are trapped in a state where they prepare to produce antibodies but cannot actually do so, they experience significant internal biological strain. The study found that Hodgkin lymphoma cells unusually activate the unfolded protein response pathway, a mechanism normally used by healthy plasma cells to manage the stress of manufacturing immunoglobulins. Since the cancer cells do not produce these antibodies, they appear to have hijacked this stress response as a specialized survival tool. This reliance on the stress pathway suggests that targeting the protein response could be a viable alternative to traditional chemotherapy.