Studying the tumor microenvironment of Hodgkin Lymphoma with scRNA-seq

Abstract

The treatment of Hodgkin lymphoma (HL) is considered a success story: cure rates surpass 80%. However, the successful treatment of HL can result in adverse side-effects later in life. Thus, there remains a need for novel therapies that result in a better quality-of-life after treatment. The tumor microenvironment (TME) affects tumor proliferation and progression. Interactions between tumor cells and their TME are being targeted as novel treatment options. A well-known inhibitory interaction in HL is PD-1 mediated inhibition of cytotoxic T-cell activity, which renders the immune system in the TME inactive and lets Hodgkin cancer cells escape immune detection. To study HL TME composition in pediatric patients, samples were analysed on a single cell level. A T-cell dominant TME marked with exhaustion markers CTLA4 and LAG3 was identified. Tumor cells were identified for seven out of eight patients using a SORT-seq strategy. Interactions between tumor cells and their TME were studied with CellChat, a method that reconstructs cell-cell interaction by computing a probability score based on scRNA-seq data. Finally, identified interactions were compared to previously published results. Both similarities and discrepancies were found, indicating that there is a likely biological difference between published Hodgkin protein data focussing on adults and pediatric scRNA-seq data that has been described here.