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The HRS cells depend on the surrounding immune cells for survival and growth. This dependence is leveraged by current treatments that target the PD\u20101\/PD\u2010L1 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\u2010cell RNA sequencing (scRNA\u2010seq) on isolated HRS cells and the immune cells from the same cHL tumors. Besides <jats:italic>TNFRSF8<\/jats:italic> (CD30), we identified other genes of cell surface proteins that are consistently overexpressed in HRS cells, such as <jats:italic>NRXN3<\/jats:italic> and <jats:italic>LRP8<\/jats:italic>, which can potentially be used as alternative targets for antibody\u2013drug conjugates or CAR T cells. Finally, we identified potential interactions by which HRS cells inhibit T cells, among which are the galectin\u20101\/CD69 and HLA\u2010II\/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\u2010immune cell interactions.<\/jats:p>","DOI":"10.1002\/hem3.149","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T06:40:12Z","timestamp":1725345612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Single\u2010cell RNA sequencing of pediatric Hodgkin lymphoma to study the inhibition of T cell subtypes"],"prefix":"10.1002","volume":"8","author":[{"given":"Jurrian\u00a0K.","family":"de Kanter","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander\u00a0S.","family":"Steemers","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0Montiel","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravian L.","family":"van Ineveld","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Blijleven","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Groenen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurianne","family":"Trabut","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijn\u00a0A.","family":"Scheijde\u2010Vermeulen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liset","family":"Westera","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auke","family":"Beishuizen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C.","family":"Rios","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Oncode Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank\u00a0C. 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