Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells, induced tumor regressions, and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

中文翻译：

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用于癌症免疫治疗的体内树突状细胞重编程


免疫疗法可以导致一些癌症患者的长期生存，但由于抗原呈递不足和免疫原性细胞从肿瘤微环境中排除，普遍的成功受到了阻碍。在这里，我们开发了一种通过腺病毒递送转录因子 PU.1、IRF8 和 BATF3 在体内重编程肿瘤细胞的方法，这使它们能够将抗原呈递为 1 型常规树突状细胞。重编程的肿瘤细胞重塑了它们的肿瘤微环境，募集和扩增了多克隆细胞毒性 T 细胞，诱导肿瘤消退，并在多种小鼠黑色素瘤模型中建立了长期的全身免疫。在人肿瘤球状体和异种移植物中，重编程为免疫原性树突状细胞的进展与免疫抑制无关，免疫抑制通常会限制免疫治疗。我们的研究为用于癌症免疫治疗的体内免疫细胞重编程的人体临床试验铺平了道路。