Tumor microenvironment differences between diagnostic and relapsed classic Hodgkin lymphoma revealed by scRNA-seq

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Classical Hodgkin lymphoma (CHL) features a complex tumor microenvironment (TME) aiding disease progression.
• The role of nonmalignant B cells in CHL relapse is not well understood.
• Hodgkin and Reed-Sternberg (HRS) cells are known to recruit immune cells.

Purpose of the Study:

• To investigate the role of nonmalignant B cells in CHL relapse.
• To identify distinct B-cell populations and their functions in relapsed CHL.
• To understand the spatial and transcriptional dynamics of the relapsed TME.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) on paired diagnostic and relapsed CHL samples.
• Validation using independent cohorts with scRNA-seq and immunohistochemistry.
• Cell-cell interaction analysis and spatial analysis by imaging mass cytometry.

Main Results:

• Early-relapse CHL shows an enrichment of naïve B cells and a reduction of memory B cells.
• Naïve B cells in early relapse express high levels of LGALS9 (galectin-9), an immunosuppressive gene.
• LGALS9+ naïve B cells interact with HAVCR2 (TIM-3)+ regulatory T cells (Tregs), forming an immunosuppressive niche.

Conclusions:

• A novel population of galectin-9-positive naïve B cells with immunoregulatory potential exists in early-relapse CHL.
• These cells contribute to an immunosuppressive TME in relapsed CHL.
• Findings offer new insights into the TME architecture in relapsed CHL.