撰文丨王聪 编辑丨王多鱼 排版丨水成文 溶瘤病毒 （ Oncolytic Viruse， OV） 是癌症治疗中一种很有前景的疗法。这些具有复制能力的病毒在肿瘤细胞中的优先复制和溶瘤作用，以及溶瘤后激活的免 疫反应，被认为是溶瘤病毒发挥抗肿瘤作用的主要原因。基于单纯疱疹病毒 （HSV） 的首个获美国 FDA 批准的溶瘤病毒疗法 Imlygic 瘤内注射治疗黑色素瘤已 取得了显著成功。 2023 年 10 月， Alexander L. Ling 等人在 Nature 期刊发表论文 【1】 ，报告了一项 first in human 的 1 期临床试验的安全性数据，41 名 复发性胶质母细胞 瘤 （rGBM） 患者接受了基于 单纯疱疹病毒 1 型的溶瘤病毒 （ oHSV ） 的治疗，该溶瘤病毒经过精心设计改造，其 仅在胶质母细胞瘤细胞内选择性复制，同 时不损害健康脑组织。这种肿瘤趋向性的溶瘤病毒利用了癌细胞的弱点：一旦感染，它就会劫持癌细胞的机制来自我复制，从而导致受感染癌细胞的死亡。该溶 瘤病毒不仅仅是癌细胞杀伤剂，它还能引发免疫原性级联反应，将免疫系统的多种成分招募到肿瘤中。结果显示， 瘤内注射 oHSV 治 ...

Core Viewpoint - The article discusses the increasing consumption of fructose and its potential health risks, particularly its role in aggravating inflammation and its association with various diseases, including cancer and metabolic disorders [2][3][4]. Group 1: Fructose Consumption and Health Risks - Fructose is a monosaccharide that has been widely used as a sweetener in beverages and processed foods, leading to a significant increase in its consumption over the past 50 years [2]. - Excessive intake of fructose is linked to various health issues, including high blood sugar, obesity, type 2 diabetes, fatty liver, cardiovascular diseases, and an increased risk of certain cancers such as colorectal, pancreatic, ovarian, and liver cancer [2][3]. - Recent studies indicate that high fructose consumption may also be associated with anxiety disorders, particularly among adolescents [2]. Group 2: Immune System Impact - The impact of fructose on the immune system, particularly its role in regulating acquired immunity and T cell immunity, has not been sufficiently studied [3][6]. - A recent study found that high fructose intake promotes the generation of effector T cells (Th1 and Th17), exacerbating inflammation and potentially worsening inflammatory bowel disease (IBD) [4][7]. - The study suggests that the common antidiabetic drug metformin can reverse the effects of high fructose intake by inhibiting mTORC1 activation and reducing reactive oxygen species (ROS) mediated TGF-β activation, thus alleviating T cell inflammation and colitis [4][9]. Group 3: Mechanisms of Fructose-Induced Inflammation - High fructose intake enhances the differentiation of Th1 and Th17 cells through a glutamine metabolism-dependent pathway that activates mTORC1, contributing to the progression of IBD [7]. - The study highlights that fructose can directly mediate immune responses and disrupt immune homeostasis, leading to increased inflammation [9]. Group 4: Fructose and Cancer Growth - Additional research indicates that fructose may indirectly promote tumor growth by enhancing lipid transfer between organs, providing cancer cells with the necessary lipids for rapid proliferation [13]. - Another study reveals that fructose inhibits the polarization of M1-like tumor-associated macrophages, promoting the development of colorectal cancer through mechanisms that do not rely on its downstream metabolites [15].