Resveratrol Enhances CAR NK Cell Function in Cellular Immunotherapy of Non-Hodgkin Lymphoma.

IF 4.5 2区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY
Xuanren Shi,Xiaoqing Wu,Feng Yang,Xiaofang Hu,Qingzheng Kang
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Abstract

Resveratrol (RSV) is a dietary polyphenolic compound with anticancer property. However, its clinical translation as an anticancer chemotherapeutic agent is hindered by multiple challenges. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising immunotherapeutic strategy against refractory malignancies. The role of RSV in CAR NK cell therapy remains unexplored. This study pioneers the investigation of RSV's role in CAR NK immunotherapy. Specially, RSV preconditioning improved CAR NK cells' resistance to oxidative stress, and augmented energetic metabolism in CAR NK cells. More importantly, the enhanced cytotoxicity against cancer cells of non-Hodgkin lymphoma (NHL) and stronger cytokine secretions were observed in RSV-treated anti-CD19 CAR NK cells. In vivo tracking revealed RSV extended CAR NK tissue residency and enhanced therapeutic efficacy in NHL xenografts. RSV-adjuvanted anti-CD19 CAR NK therapy achieved an obvious reduction in intraperitoneal tumor burden and improvement in the mice survival. Our mechanistic investigation revealed that nuclear factor erythroid 2-related factor 2 (NRF2) serves as a critical mediator in RSV-induced functional augmentation of CAR NK cells. These findings established RSV as a potential polyphenol adjuvant capable of improving CAR NK therapy, providing a translatable strategy for polyphenols to overcome current limitations in cancer therapy.
白藜芦醇在非霍奇金淋巴瘤细胞免疫治疗中增强CAR - NK细胞功能。
白藜芦醇(Resveratrol, RSV)是一种具有抗癌特性的膳食多酚化合物。然而,其作为抗癌化疗药物的临床转化受到多重挑战的阻碍。嵌合抗原受体(CAR)自然杀伤(NK)细胞疗法已成为一种有前途的免疫治疗策略,用于治疗难治性恶性肿瘤。RSV在CAR - NK细胞治疗中的作用尚不清楚。这项研究开创了RSV在CAR - NK免疫治疗中的作用的研究。特别是,RSV预处理提高了CAR - NK细胞对氧化应激的抵抗力,增强了CAR - NK细胞的能量代谢。更重要的是,rsv处理的抗cd19 CAR - NK细胞对非霍奇金淋巴瘤(NHL)癌细胞的细胞毒性增强,细胞因子分泌增强。体内跟踪显示,RSV延长了CAR - NK组织驻留时间,增强了NHL异种移植物的治疗效果。rsv辅助抗cd19 CAR - NK治疗可明显减轻小鼠腹膜内肿瘤负荷,提高小鼠生存率。我们的机制研究表明,核因子红细胞2相关因子2 (NRF2)在rsv诱导的CAR NK细胞功能增强中起着关键的中介作用。这些发现表明RSV是一种潜在的多酚佐剂,能够改善CAR - NK治疗,为多酚克服目前癌症治疗中的局限性提供了一种可翻译的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Nutrition & Food Research
Molecular Nutrition & Food Research 工程技术-食品科技
CiteScore
8.70
自引率
1.90%
发文量
250
审稿时长
1.7 months
期刊介绍: Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.
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