撰文丨王聪 编辑丨王多鱼 排版丨水成文 免疫检查点阻断 （ICB） 疗法通过唤醒人体自身的免疫系统来对抗肿瘤，从而彻底改变了癌症的治疗方式。然而，许多癌症患者仍对这种疗法无响应，且有相当 一部分患者会遭受严重的副作用，尤其是肠道和肺部的损伤。最近的研究表明，我们体内数以万亿计的微生物组成的肠道微生物群，在 ICB 疗法的有效性和安全 性方面发挥着至关重要的作用。 2025 年 8 月 22 日，浙江大学 周民 教授团队在 Cell 子刊 Cell Biomaterials 上发表了题为： Enhancing anti-tumor immunity and reducing toxicity: A medicine and food homology formula for ICB therapy 的研究论文。 该研究开发了一种 药食同源 配方——使用 微球 （ MS ） 共载 普通小球藻 （ C. vulgaris ） 和 黄芪多糖 （APS ） —— CV /APS-MS ，有助于在 改善免疫检 查点阻断疗法的癌症免疫治疗效果的同时，减少 免疫相关不良事件 （irAE） 风险，为更安全、更有效的免疫检查点阻 ...

Core Viewpoint - The emergence of immunotherapy has significantly changed the landscape of cancer treatment, but resistance to immunotherapy remains a major obstacle for its broader clinical application. Recent studies indicate that gut microbiota can enhance the efficacy of immunotherapy by modulating anti-tumor immunity [2]. Group 1: Research Findings - A study published by Professor Xu Ruihua's team from Sun Yat-sen University on July 24, 2025, in the journal Cancer Cell, demonstrates that the gut bacterium Alistipes finegoldii can enhance the efficacy of immunotherapy against solid tumors [3][4]. - The research found that a higher abundance of Alistipes finegoldii is associated with improved responses to immunotherapy, particularly enhancing the efficacy of anti-PD-1 monoclonal antibodies in solid tumor models [8]. - Alistipes finegoldii activates the CXCL16-CXCR6 signaling axis to boost anti-tumor immune responses, with lipoproteins derived from Alistipes finegoldii triggering the TLR2-NF-κB-CXCL16 signaling pathway [7][8]. Group 2: Mechanism of Action - The mechanism involves lipoproteins from Alistipes finegoldii binding to Toll-like receptor 2 (TLR2), activating the NF-κB signaling pathway, which enhances the expression of CXCL16 in CCR7+ conventional dendritic cells [7]. - The released CXCL16 aids in recruiting CXCR6+ CD8+ T cells to the tumor microenvironment (TME), effectively inhibiting tumor growth [7][8]. Group 3: Implications for Treatment - Overall, the findings suggest that combining Alistipes finegoldii with immunotherapy could represent a new strategy for treating solid tumors [10].

Core Viewpoint - The study highlights the impact of gut microbiota dysbiosis induced by brain tumors on the efficacy of immunotherapy, suggesting that dietary supplementation with tryptophan can restore gut microbiota and significantly enhance the immune response through T cell circulation [2][11][14]. Group 1: Research Background - The influence of gut microbiota on various tumors, particularly gastrointestinal tumors, is recognized, but its effects on brain tumors remain largely unexplored [2][6]. - Glioblastoma (GBM) is known for its poor prognosis and limited survival rate improvements despite various treatments, attributed to unique characteristics of the tumor microenvironment [4][5]. Group 2: Research Findings - The research utilized a GBM mouse model and employed 16S rRNA sequencing to analyze changes in gut microbiota during tumor progression, finding that tryptophan supplementation could reverse these changes [9]. - Tryptophan supplementation not only restored gut microbiota balance but also significantly improved survival rates in mouse models and enhanced the effectiveness of immunotherapy [9][13]. Group 3: Key Microbial Insights - Among the gut bacteria responding positively to tryptophan, Duncaniella dubosii emerged as a key contributor to the immune modulation effects of tryptophan [10][13]. - The study emphasizes the potential of targeting gut microbiota modulation to improve cancer immunotherapy outcomes, particularly through mechanisms involving T cell regulation [14].

Core Viewpoint - The study highlights the role of gut microbiota, specifically the metabolite urocanic acid (UCA), in enhancing the efficacy of cancer immunotherapy when combined with tyrosine kinase inhibitors (TKIs) [3][8][11]. Group 1: Research Findings - The research demonstrates that TKIs increase the abundance of the gut bacterium Muribaculum gordoncarteri and its metabolite UCA, which enhances the response to immune checkpoint blockade (ICB) therapy [8][9]. - UCA interacts with IκBα to inhibit NF-κB activation in endothelial cells, thereby reducing the recruitment of myeloid-derived suppressor cells (MDSCs) mediated by CXCL1 [9][11]. - Higher levels of UCA and Muribaculum gordoncarteri are found in the feces of patients who respond to ICB therapy compared to non-responders, suggesting their potential as predictive biomarkers for treatment response [8][9][11]. Group 2: Implications for Cancer Treatment - The findings indicate that the interaction between TKIs and gut microbiota could be a crucial factor in improving cancer treatment outcomes, particularly for patients who currently do not respond well to existing therapies [7][9]. - Understanding the mechanisms by which UCA enhances ICB therapy could lead to new strategies for increasing the effectiveness of cancer immunotherapy [3][11].

Core Viewpoint - The article discusses a study published in Nature Metabolism that highlights the potential of Nicotinamide to accelerate recovery in mild to moderate COVID-19 patients and its role in modulating gut microbiota changes associated with the virus [2][12]. Group 1: Nicotinamide and COVID-19 - Nicotinamide is essential for the production of NAD+, a key coenzyme in cellular energy metabolism, which decreases during viral infections, particularly COVID-19 [5]. - The study indicates that during acute inflammation caused by SARS-CoV-2, tryptophan metabolism is enhanced, leading to increased kynurenine levels, which is a critical intermediate in the NAD+ synthesis pathway [5]. - COVID-19 is closely linked to gut microbiota dysbiosis, characterized by reduced microbial diversity and beneficial species, which is associated with increased inflammation and immune dysregulation [5]. Group 2: Research Findings - Previous research showed that tryptophan helps maintain gut microbiota homeostasis, and supplementation with Nicotinamide has strong, microbiota-dependent anti-inflammatory effects [6]. - The study developed a pH-dependent matrix tablet formulation for Nicotinamide, designed to release in the lower small intestine and colon, ensuring systemic supply and targeting gut microbiota [6]. - The COVit-2 trial involved 900 symptomatic COVID-19 patients and demonstrated that 57.6% of those treated with Nicotinamide recovered from physical decline by week 2, compared to 42.6% in the placebo group [7]. Group 3: Clinical Implications - The changes in gut microbiome characteristics correlated with clinical efficacy, suggesting that Nicotinamide can regulate fecal microbiota changes associated with SARS-CoV-2 infection [8]. - Follow-up after 6 months indicated that those who responded to Nicotinamide treatment had a lower incidence of post-COVID syndrome compared to the placebo group [8]. - Throughout the study, no safety risks related to Nicotinamide treatment were reported [8].