biostudies-literatureGottschlich AEuropean Research Council1536-1552https://www.ebi.ac.uk/biostudies/studies/S-EPMC12002222biostudies-literatureUnknown145(14)<h4>Abstract</h4>The success of targeted therapies for hematological malignancies has heralded their potential as both salvage treatment and early treatment lines, reducing the need for high-dose, intensive, and often toxic chemotherapeutic regimens. For young patients with classic Hodgkin lymphoma (cHL), immunotherapies provide the possibility to lessen long-term, treatment-related toxicities. However, suitable therapeutic targets are lacking. By integrating single-cell dissection of the tumor landscape and an in-depth, single-cell-based off-tumor antigen prediction, we identify CD86 as a promising therapeutic target in cHL. CD86 is highly expressed on Hodgkin and Reed-Sternberg cancer cells and cHL-specific tumor-associated macrophages. We reveal CD86-CTLA-4 as a key suppressive pathway BloodDissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.PMC12002222756017101100460101124203Hoffmann GVOner AEndres SMesquita PBrockelmann PJGartig JSimnica DTsiverioti CABaran-Marszak FBriukhovetska DStock SGrunmeier RHellmuth JIgl VThomas MLorenzini TMichaelides SSchulz HMulkers MCarlini ENandi SKaiser RTrefny MPStrzalkowski TNicolai LGelebart PFJanert TAFairley SDDi Fina LKlapper WMegens RTAFrenz-Wiessner SMarr CPiseddu IReinke SKobold SMuller PJvon Bergwelt-Baildon MGottschlich AKlein CKavaka VThelen MRosenwald AJobst JMarkl FBeltran EBrabenec RfalseDissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.<h4>Abstract</h4>The success of targeted therapies for hematological malignancies has heralded their potential as both salvage treatment and early treatment lines, reducing the need for high-dose, intensive, and often toxic chemotherapeutic regimens. For young patients with classic Hodgkin lymphoma (cHL), immunotherapies provide the possibility to lessen long-term, treatment-related toxicities. However, suitable therapeutic targets are lacking. By integrating single-cell dissection of the tumor landscape and an in-depth, single-cell-based off-tumor antigen prediction, we identify CD86 as a promising therapeutic target in cHL. CD86 is highly expressed on Hodgkin and Reed-Sternberg cancer cells and cHL-specific tumor-associated macrophages. We reveal CD86-CTLA-4 as a key suppressive pathway 2025-01-01T00:00:00Z2025 Apr2026-06-02T06:44:02.493Z2026-04-15T03:14:51.793ZS-EPMC120022224017884310.1182/blood.2023022197