MS-20 增强抗 PD1 抗体与肠道微生物群相关的抗肿瘤作用。
MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody.
发表日期:2024
作者:
Pei-Jung Lee, Chien-Min Hung, Ai-Jen Yang, Cheng-Yu Hou, Hung-Wen Chou, Yi-Chung Chang, Wen-Cheng Chu, Wen-Yen Huang, Wen-Chih Kuo, Chia-Chun Yang, Kuo-I Lin, Kuo-Hsuan Hung, Li-Chun Chang, Kang-Yun Lee, Han-Pin Kuo, Kung-Ming Lu, Hsin-Chih Lai, Ming-Liang Kuo, Wan-Jiun Chen
来源:
Gut Microbes
摘要:
癌症免疫疗法通过阻断免疫检查点并激发免疫力来对抗癌症,被认为是一种有前途的癌症治疗策略,但其疗效在患者之间似乎存在差异。操纵肠道微生物群是增强免疫疗法疗效的潜在策略。在此,我们报道 MS-20,也称为“Symbiota®”,是一种后生元,包含由多种益生菌和酵母菌株发酵的大豆培养基产生的丰富微生物代谢物,与异种移植小鼠模型中的抗程序性细胞死亡 1 (PD1) 抗体。从机制上讲,MS-20 通过增加效应 CD8 T 细胞和下调由肠道微生物群介导的 PD1 表达来重塑免疫肿瘤微环境。接受 MS-20 治疗的小鼠的粪便微生物群移植 (FMT) 增加了 CD8 T 细胞对肿瘤微环境的浸润,并与抗 PD1 治疗相结合,显着提高了抗肿瘤活性。值得注意的是,MS-20 治疗后溴瘤胃球菌的丰度增加,与体内肿瘤负荷的减少和 CD8 T 细胞浸润呈正相关。此外,一项离体研究表明,MS-20 可以改变癌症患者的微生物群组成,从而产生与免疫治疗有利反应相关的独特代谢途径。总体而言,MS-20 可以作为一种有前途的佐剂,用于增强免疫检查点介导的抗肿瘤治疗的功效。
Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8+ T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8+ T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8+ T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.