Single-cell RNA sequencing of pediatric Hodgkin lymphoma to study the inhibition of T cell subtypes.

Autor: de Kanter JK; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Steemers AS; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Gonzalez DM; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., van Ineveld RL; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Blijleven C; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands.; Present address: University of Copenhagen Copenhagen Denmark., Groenen N; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Trabut L; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Scheijde-Vermeulen MA; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands., Westera L; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands., Beishuizen A; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands., Rios AC; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Holstege FCP; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands., Brandsma AM; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands.; Present address: Sanquin Blood Bank Amsterdam the Netherlands., Margaritis T; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands., van Boxtel R; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.; Oncode Institute Utrecht The Netherlands., Meyer-Wentrup F; Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands.
Jazyk: angličtina
Zdroj: HemaSphere [Hemasphere] 2024 Sep 02; Vol. 8 (9), pp. e149. Date of Electronic Publication: 2024 Sep 02 (Print Publication: 2024).
DOI: 10.1002/hem3.149
Abstrakt: Pediatric classic Hodgkin lymphoma (cHL) patients have a high survival rate but suffer from severe long-term side effects induced by chemo- and radiotherapy. cHL tumors are characterized by the low fraction (0.1%-10%) of malignant Hodgkin and Reed-Sternberg (HRS) cells in the tumor. The HRS cells depend on the surrounding immune cells for survival and growth. This dependence is leveraged by current treatments that target the PD-1/PD-L1 axis in cHL tumors. The development of more targeted therapies that are specific for the tumor and are therefore less toxic for healthy tissue compared with conventional chemotherapy could improve the quality of life of pediatric cHL survivors. Here, we applied single-cell RNA sequencing (scRNA-seq) on isolated HRS cells and the immune cells from the same cHL tumors. Besides TNFRSF8 (CD30), we identified other genes of cell surface proteins that are consistently overexpressed in HRS cells, such as NRXN3 and LRP8 , which can potentially be used as alternative targets for antibody-drug conjugates or CAR T cells. Finally, we identified potential interactions by which HRS cells inhibit T cells, among which are the galectin-1/CD69 and HLA-II/LAG3 interactions. RNAscope was used to validate the enrichment of CD69 and LAG3 expression on T cells near HRS cells and indicated large variability of the interaction strength with the corresponding ligands between patients and between tumor tissue regions. In conclusion, this study identifies new potential therapeutic targets for cHL and highlights the importance of studying heterogeneity when identifying therapy targets, specifically those that target tumor-immune cell interactions.
Competing Interests: The authors declare no conflicts of interest.
(© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)
Databáze: MEDLINE
Externí odkaz: