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.
免疫疗法可使一些癌症患者长期存活，但由于抗原呈递不足以及肿瘤微环境中免疫原性细胞的排斥，免疫疗法的普遍成功一直受到阻碍。在这里，我们开发了一种方法，通过腺病毒递送转录因子PU.1、IRF8和BATF3，在体内对肿瘤细胞进行重编程，使它们能像1型常规树突状细胞一样呈递抗原。重编程的肿瘤细胞重塑了肿瘤微环境，招募并扩增了多克隆细胞毒性T细胞，诱导了肿瘤消退，并在多种小鼠黑色素瘤模型中建立了长期的全身免疫力。在人类肿瘤球体和异种移植物中，重编程为免疫原性树突状细胞的过程不受免疫抑制的影响，而免疫抑制通常会限制免疫疗法。我们的研究为体内免疫细胞重编程用于癌症免疫疗法的人体临床试验铺平了道路。
参考文献
Ascic E, Åkerström F, Sreekumar Nair M, Rosa A, Kurochkin I, Zimmermannova O, Catena X, Rotankova N, Veser C, Rudnik M, Ballocci T, Schärer T, Huang X, de Rosa Torres M, Renaud E, Velasco Santiago M, Met Ö, Askmyr D, Lindstedt M, Greiff L, Ligeon LA, Agarkova I, Svane IM, Pires CF, Rosa FF, Pereira CF. In vivo dendritic cell reprogramming for cancer immunotherapy. Science. 2024 Sep 5:eadn9083.
