肿瘤细胞治疗研究
英文原题：Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.
Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.
血液系统恶性肿瘤靶向治疗的成功预示着其作为挽救治疗和早期治疗方案的潜力，减少了对高剂量、强化且往往有毒性的化疗方案的需求。
针对血液系统恶性肿瘤的靶向治疗的成功预示着其作为挽救治疗和早期治疗方案的潜力，减少了对高剂量、强化且往往有毒性的化疗方案的需求。对于年轻的经典霍奇金淋巴瘤（cHL）患者，免疫疗法提供了减轻长期治疗相关毒性的可能性。然而，合适的治疗靶点仍然缺乏。通过整合肿瘤微环境的单细胞解析和基于单细胞的深入肿瘤外抗原预测，我们确定CD86是cHL中一个有前景的治疗靶点。CD86在霍奇金和Reed-Sternberg癌细胞以及cHL特异性肿瘤相关巨噬细胞上高表达。我们揭示CD86-CTLA-4是cHL中驱动T细胞耗竭的关键抑制通路。靶向CD86的细胞疗法在体外和体内均具有非凡的疗效，并且在免疫健全小鼠模型中安全，未在脓毒症模型中损害细菌宿主防御。我们的结果证明了抗CD86免疫疗法治疗cHL的潜在价值。
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 in cHL, driving T-cell exhaustion. Cellular therapies targeting CD86 had extraordinary efficacy in vitro and in vivo and were safe in immunocompetent mouse models without compromising bacterial host defense in sepsis models. Our results prove the potential value of anti-CD86 immunotherapies for treating cHL.
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