放疗与诱导型AAV免疫治疗平台协同作用，规划局部和全身抗肿瘤免疫，这一成果由纳瓦拉大学Juan Dubrot研究小组经过不懈努力而取得。相关论文于2026年3月23日发表于国际顶尖学术期刊《癌细胞》杂志上。

为了克服这一限制，该课题组观察到RT通过对载体片段的表观遗传修饰增强了腺相关载体（AAVs）的肿瘤转导。该课题组研究人员设计了一个基于AAV的平台，通过干扰素（IFN）诱导的启动子传递免疫刺激细胞因子，允许在辐照肿瘤中对转基因表达进行空间控制。与本构系统相反，局部递送编码诱导型IL-12 （AAV-iIL12）的载体实现了细胞因子的有效生产，而没有明显的毒性。RT和AAV-iIL12联合产生高度免疫刺激的肿瘤微环境（TME），以IFNγ和FAS依赖的方式导致局部和全身抗肿瘤反应，能够克服常见的免疫逃避机制。他们的工作表明，辐射结合基于AAV的免疫基因传递是一种有效而安全的治疗癌症的方法。

据介绍，放疗（RT）可以启动免疫系统对抗癌症，但由于伴随的免疫抑制因子的诱导，往往不能产生有效的抗肿瘤反应。

附：英文原文

Title: Radiotherapy synergizes with an inducible AAV-based immunotherapy platform to program local and systemic antitumor immunity

Author: Sonia Marco, Myriam Fernández, Beatriz Honorato, Nerea Juanarena, Cristina Sainz, Ainhoa Andueza, David J. Gould, Seth Anderson, Carlos de Andrea, Paulo Pérez Domínguez, Paolo Wong, Carlos Vásquez, Irene Narinda, Carmen Unzu, Sergio Isola, Beatriz Tavira, Mikel Ariz, Gracián Camps, Miguel F. Sanmamed, Julián Pardo, Sara Labiano, Marta M. Alonso, Javier Marco-Sanz, Elizabeth Guruceaga, María Collantes, Jon Ander Simón, Iván Peuelas, Joaquín Fernández-Irigoyen, Enrique Santamaría, Jesús Prieto, Juan Dubrot

Issue&Volume: 2026-03-23

Abstract: Radiotherapy (RT) can prime the immune system against cancer but often fails to generate effective antitumor responses due to concomitant induction of immunosuppressive factors. To overcome this limitation, we built upon the observation that RT enhances adeno-associated vectors (AAVs) tumor transduction through the epigenetic modification of vector episomes. We designed an AAV-based platform to deliver immunostimulatory cytokines through an interferon (IFN)-inducible promoter that allows for spatial control of transgene expression into irradiated tumors. As opposed to a constitutive system, local delivery of a vector encoding for inducible IL-12 (AAV-iIL12) achieves an efficient production of the cytokine without significant toxicity. Combination of RT and AAV-iIL12 generates a highly immunostimulatory tumor microenvironment (TME) leading to robust local and systemic antitumor responses in an IFNγ- and FAS-dependent manner, able to overcome common immune-evasion mechanisms. Our work shows that radiation coupled with AAV-based immune-gene delivery is an efficient and safe approach to treat cancer.

DOI: 10.1016/j.ccell.2026.02.013

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(26)00111-X