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High-dose VitC plus oncolytic adenoviruses enhance immunogenic tumor cell death and reprogram tumor immune microenvironment
Molecular Therapy ( IF 12.4 ) Pub Date : 2021-09-20 , DOI: 10.1016/j.ymthe.2021.09.015
Jinhu Ma 1 , Chunxue Zhang 1 , Gang Shi 1 , Dan Yue 2 , Yongheng Shu 1 , Shichuan Hu 1 , Zhongbing Qi 1 , Yanwei Chen 1 , Bin Zhang 1 , Yong Zhang 1 , Anliang Huang 3 , Chao Su 1 , Yan Zhang 4 , Hongxin Deng 1 , Ping Cheng 1
Affiliation  

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.



中文翻译:

高剂量 VitC 加溶瘤腺病毒可增强免疫原性肿瘤细胞死亡并重新编程肿瘤免疫微环境

临床前和临床研究已经验证了几种溶瘤病毒 (OV) 的抗肿瘤作用。然而,当 OV 作为单一疗法给药时,它们的功效是有限的。联合疗法是未来溶瘤病毒疗法的一个有前途的方向。高剂量的维生素 C (VitC) 通过触发大量活性氧 (ROS) 的积累发挥抗癌作用。OV 可诱导免疫原性肿瘤细胞死亡并引发抗肿瘤免疫反应。ROS 在免疫原性细胞死亡 (ICD) 中发挥重要作用。本研究旨在探讨高剂量 VitC 与溶瘤腺病毒 (oAds) 联合使用是否具有协同抗肿瘤作用。高剂量 VitC 通过增强免疫原性肿瘤细胞死亡与 oAd 协同抗肿瘤。大剂量 VitC 和 oAds 的联合治疗显着增加了肿瘤微环境 (TME) 中的 T 细胞数量,并促进了 T 细胞的活化。此外,联合治疗的抗肿瘤作用为 CD8+ T 细胞依赖性。此外,大剂量 VitC 和 oAds 的联合治疗重新编程了免疫抑制性 TME。我们的研究为 OV 的联合治疗提供了一种新策略。

更新日期:2021-09-20
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