撰文丨王聪 编辑丨王多鱼 排版丨水成文 胶质母细胞瘤 （GBM） 是成年人中最常见、最具侵袭性的恶性脑肿瘤。胶质母细胞瘤 表现出显著的异质 性， 患者在确诊后通常只能存活 12-18 个月。 尽管经过了几十年的研究，但该疾病尚无治愈方法，而且 已批准的治疗方法 （例如手术、放疗和化疗） 在延长预期寿命方面效果有限。 胶质母细胞瘤的 肿瘤微环境 （TME） 复杂，以 胶质母细胞瘤干细胞 （GSC） 为主，并有 肿瘤相关巨噬 细胞 （TAM） 浸润，且存在异常的代谢途径。 乳酸 （ Lactate ） 是一种关键的糖酵解代谢物，可促进 肿瘤进展；然而，胶质母细胞瘤的肿瘤微环境中 乳酸转运 和 乳酸化修饰 的作用机制仍不清楚。 2026 年 1 月 6 日，南京医科大学基础医学院 汪秀星 教授、北卡罗来纳大学教堂山分校 Jeremy N. Rich 教授、南京医科大学基础医学院 张茜 副教授、南京医科大学公共卫生学院 钱旭 教授、南京医科大学第一 附属医院 张军霞 教授作为共同通讯作者 （ 李大奇 、 崔高源 、 Kailin Yang 、 陆晨飞 、 江雨韩 、 张乐 为论文共同第一作者） ，在 Nature 子 ...

撰文丨王聪 编辑丨王多鱼 2025 年 12 月 10 日，南加州大学 王荣福 教授团队 （ 柳鑫 博士为论文第一作者） 在 Science 子刊 Science Translational Medicine 上发表了题为： ZAP327 signaling domain–driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse models 的研究论文。 该研究开发了一种 ZAP327 信号结构域驱动的新型 CAR 结构 ，基于这种 CAR 结构的 CAR-T 细胞疗法 显著降低了细胞因子释放、减少了 T 细胞耗竭，在小鼠模型中产生强大且持久的抗肿瘤免疫反应。这代表 了 CAR-T 细胞疗法的有前景的改进方向。 当前的 CAR 结构通常包含四个主要组成部分：一个抗原结合域、一个铰链区和跨膜结构域、一个胞内共刺 激结构域、以及一个 T 细胞信号转导结构域。 排版丨水成文 CAR-T 细胞疗法 在血液类癌症中已产生令人瞩目的临床疗效，证明了这种合成 T 细胞信号受体是产生治 疗性抗肿瘤免 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 饮食限制 （ dietary restriction，DR ） ，是一类限制热量摄入但不造成营养不良的饮食方案，包括禁食、模拟禁食、低升糖指数饮食等，可延长哺乳动物寿命， 并延 缓包括癌症在内的年龄相关疾病的发生，但其背后的具体机制尚不完全清楚。 2025 年 12 月 9 日，美国 范安德研究中心的研究人员在 Nature 子刊 Nature Metabolism 上发表了题为： Dietary restriction reprograms CD8 + T cell fate to enhance anti-tumour immunity and immunotherapy responses 的研究论文。 该研究表明， 饮食限制 引起的 酮体代谢变化 （产生更多的 β-羟基丁酸 ） 可重编程肿瘤微环境中的 CD8 + T 细胞命运和功能，从而增强抗肿瘤免疫和免疫治疗 响应。 那么，饮食限制是如何实现这一神奇转变的呢？答案在于—— 酮体代谢 。 当身体处于饮食限制状态时，肝脏会产生更多的 β-羟基丁酸 （βOHB） 等酮体。研究团队发现，这些酮体能够作为 CD8 + ...

2025 年 11 月 27 日，清华大学 江鹏 课题组 （ 吴珺 、 李根 、 周嘉文 为论文共同第一作者） 在 Cell 子刊 Developmental Cell 上发表了题为： Vitamin B6 preserves the stemness-like phenotypes and antitumor ability of CD8 + T cells 的研究论文。 该研究揭示了饮食来源的代谢小分子 维生素 B6 能够促进肿瘤内浸润 CD8 + T 细胞 的干细胞样特征来增强 抗肿瘤免疫功能，并且表现出维生素 B6 在肿瘤免疫治疗中的临床应用潜力。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 肿瘤浸润淋巴细胞通常功能失调，但其通过尚不明确的机制表现出干细胞样行为。 肿瘤浸润淋巴细胞通常功能失调，但通过尚不明确的机制表现出干细胞样行为。在这项最新研究中，研究 团队发现，给予 维生素 B6 或其活性形式—— 磷酸吡哆醛 （PLP） ，能使小鼠和人类的 CD8 + T 细胞 具 备更强的持久性、干细胞样的表型以及清除肿瘤的能力。 通过吡哆醛激酶 （PDXK） 杂合性降低磷酸吡哆 醛 （PLP） 水平，会导致肿瘤 ...

Core Insights - The study published by the team led by Academician Dong Chen from Westlake University in the journal Science highlights the role of Ms4a7 expression in cDC1 cells in promoting cross-activation of CD8+ T cells against tumors [2] - The absence of Ms4a7 in cDC1 cells impairs the specific CD8+ T cell response targeting tumors and weakens T cell immunity during bacterial and viral infections [2][4] - Human data analysis indicates that infiltration of MS4A7-expressing cDC1 cells is associated with enhanced CD8+ T cell tumor immunity and improved patient survival rates [2][4] Group 1 - cDC1 cells capture antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate antigen-specific CD8+ T cell immune responses [3] - The study found that Ms4a7 expression is upregulated in cDC1 cells upon tumor antigen uptake or exposure to external stimuli, which is essential for their cross-presentation capability [4] - Ms4a7 is located in antigen-processing vesicles, facilitating steps in the antigen presentation process without altering upstream uptake or degradation [6] Group 2 - The research reveals how tumor microenvironment signals regulate Ms4a7 expression in cDC1, enhancing their cross-presentation ability and CD8+ T cell activation [6] - In human cancers, the expression of MS4A7 correlates with robust interactions between cDC1 and T cells, leading to favorable clinical outcomes [6]

Core Insights - The study published in Nature Immunology reveals that chemotherapy-induced CA-repeat DNA fragments in breast cancer can trigger antitumor immune responses [3][4]. - The research highlights the relationship between genomic instability and immune regulation, emphasizing the therapeutic potential of CA-rich DNA in enhancing antitumor immunity [7]. Group 1 - The research team demonstrated that in tumors with low expression of MSH2, DNA fragments rich in CA, generated by DNA-damaging chemotherapy, preferentially bind with cGAS, leading to the formation of biomolecular condensates in the cytoplasm and triggering antitumor immune responses [7]. - In contrast, DNA fragments lacking CA released from tumors with high MSH2 expression activate AIM2, resulting in immune suppression through the upregulation of PD-L1 and IDO [7]. - The study found that the increase in CA-rich DNA fragments post-chemotherapy correlates with a rise in tumor antigen-responsive T cells and better chemotherapy responses [7]. Group 2 - The injection of CA-rich DNA fragments into tumors enhances antitumor immunity in PyMT allograft tumors [7]. - Different tumor DNA fragments can elicit opposing immune responses based on their preference for different sensors [7].

Core Viewpoint - The research highlights the immune-regulating properties of Zeaxanthin, a nutrient found in leafy vegetables and corn, which enhances CD8+ T cell function and improves anti-tumor immunity, indicating its potential as a dietary supplement in cancer therapy [3][10]. Group 1: Research Findings - Zeaxanthin is identified as an immune modulator that enhances the function of CD8+ effector T cells, thereby increasing anti-tumor immunity [3][10]. - Oral supplementation of Zeaxanthin improves the efficacy of anti-PD-1 immune checkpoint inhibitors and enhances the cytotoxicity of TCR-engineered CD8+ T cells against tumor cells [9][10]. - The study utilized a "blood nutrient" library to identify dietary nutrients that influence CD8+ T cell function, revealing that trans-18:1 fatty acid (TVA) also promotes CD8+ T cell activity and response to immunotherapy [6][8]. Group 2: Mechanisms of Action - Zeaxanthin enhances T cell receptor (TCR) signaling on CD8+ T cells, improving their functional response [9][10]. - The research indicates that the structural isomer Lutein does not exhibit the same immune-enhancing effects as Zeaxanthin, underscoring the unique properties of Zeaxanthin [8][10]. - The findings suggest that dietary components can play a significant role in modulating immune responses, particularly in the context of cancer treatment [5][12].

Core Viewpoint - The source of dietary fat significantly influences anti-tumor immunity in obese individuals, with animal fats impairing immune response and promoting tumor growth, while plant fats do not have this negative effect [5][7][9]. Group 1: Research Findings - A study published in Nature Metabolism indicates that high-fat diets based on animal fats (lard, beef tallow, or butter) weaken anti-tumor immunity in obese mice and accelerate tumor growth [5][7]. - In contrast, high-fat diets based on plant oils (coconut oil, palm oil, or olive oil) do not exhibit this detrimental effect, with palm oil even enhancing anti-tumor immunity and slowing tumor growth in obese mice [5][7][9]. - The research highlights that the metabolic byproducts of animal fats, particularly long-chain acylcarnitines, strongly inhibit NK and CTL cells, leading to impaired immune function [9]. Group 2: Implications for Cancer Treatment - The findings suggest that dietary modifications, such as replacing animal fats with plant oils, could be beneficial for obese cancer patients undergoing treatment, potentially lowering their cancer risk [5][6][9]. - The study emphasizes the importance of dietary fat composition in maintaining a healthy immune system and improving treatment outcomes for obese individuals with cancer [9].

Core Viewpoint - The research indicates that social interaction in mice can suppress breast cancer progression through a specific neural circuit, providing a potential theoretical basis for clinical applications of social support in tumor treatment [4][10]. Summary by Sections Research Findings - Social interaction activates neural circuits that inhibit breast cancer progression [8] - ACC Glu neurons are crucial for the anti-tumor effects of social interaction [8] - The ACC Glu → BLA Glu circuit mediates the anti-tumor benefits of social interaction [8] - Artificial activation of the social interaction circuit can enhance anti-tumor immune responses [8] Implications - The study suggests that social interaction may influence tumor progression by modulating sympathetic nerve activity and norepinephrine release, potentially reshaping anti-tumor immunity [6][10].

Core Viewpoint - Exercise is recognized as a significant factor in reducing cancer risk, enhancing the survival of cancer patients, and improving treatment outcomes, particularly through its effects on the gut microbiome and immune response [2][4][6]. Group 1: Research Findings - A study published in the journal Cell indicates that exercise induces the production of the gut microbiota metabolite formate, which enhances CD8 T cell antitumor immunity and improves the efficacy of cancer immunotherapy [3][4]. - The research highlights that the gut microbiome's metabolic products, rather than the microbiome itself, are crucial for the antitumor effects of exercise [9][10]. - The study identifies Nrf2 as a key mediator in the enhancement of Tc1 cell function driven by formate, both in vitro and in vivo [11]. Group 2: Implications for Cancer Treatment - The findings suggest that high-producing formate gut microbiota in humans can enhance tumor suppression and promote robust antitumor Tc1 immune responses, indicating formate as a potential biomarker for enhancing Tc1-mediated antitumor immunity [12][15]. - The research opens avenues for developing treatment strategies that combine exercise with microbiota-derived metabolites, particularly focusing on Nrf2 agonists like formate for patients resistant to immune checkpoint inhibitors [16][17].