Classic Hodgkin lymphoma (cHL) is a B-cell–derived lymphoma that is unique among lymphoid malignancies due to its complex tumor microenvironment, which is dominated by dysregulated immune cells, and the presence of rare Hodgkin and Reed–Sternberg (HRS) tumor cells that comprise approximately 1% of the total tumor mass.
Despite major therapeutic advances, detailed molecular characterization of HRS cells remains technically challenging, limiting our understanding of cHL pathobiology.
To address this, we developed a workflow combining FACS index sorting of HRS cells with single-cell RNA sequencing. In parallel, we perform single-cell profiling of matched tumor microenvironment samples, enabling integrated analysis of whole transcriptomes, surface protein expression, and T-cell and B-cell receptor repertoires.
This approach allows us to dissect inter- and intratumoral heterogeneity in cHL at single-cell resolution across both malignant and non-malignant compartments.
Ultimately, our work aims to identify key molecular programs and interaction patterns in HRS cells and their microenvironment that contribute to therapy resistance and relapse, providing a foundation for improved treatment strategies and prognostic assessment in Hodgkin lymphoma.
Frederik Schramm, Sophie Klotz, Bettina Budeus, Lilian K. Beeck, Marc A. Weniger, Paul J. Bröckelmann, Ralf Küppers