Zhang Jiayu, Yang Jinneng, Luo Jinyan, Wu Weili, Luo Haidan, Wei Wenxia, Lyu Haimei, Wang Yuzhi, Yi Hairong, Zhang Yijing, Fan Zongmin, Lyu Haiwen, Kanakaveti Vishnu Priya, Qin Baifu, Yuan Ping, Yang Runxiang, Zhang Haipeng, Zuo Tao, Felsher Dean W, Lee Mong-Hong, Li Kai
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Nat Commun. 2025 Apr 7;16(1):3315. doi: 10.1038/s41467-025-58407-z.
Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus. VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus (L. acidophilus) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus. L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy.
溶瘤病毒（OVs）在癌症治疗方面具有前景。然而，其抗肿瘤疗效有限。微生物群在癌症治疗中起着关键作用，但其对溶瘤病毒疗法的影响尚不清楚。在此，我们表明，在雌性小鼠模型中，缺乏微生物群时，VSVΔ51对肝细胞癌具有更高的抗肿瘤疗效。VSVΔ51感染会导致微生物群失调，增加大多数肠道细菌的丰度，同时减少共生的乳酸杆菌。VSVΔ51通过IL6-JAK-STAT3信号通路降低与嗜酸乳杆菌（L. acidophilus）CdpA细胞壁蛋白结合的SLC20A1的肠道表达，从而减弱嗜酸乳杆菌的附着和定殖。补充嗜酸乳杆菌可通过恢复被VSVΔ51破坏的肠道屏障完整性和微生物群稳态，赋予对VSVΔ51的敏感性。在这项研究中，我们表明，针对微生物群稳态在改善溶瘤病毒疗法的治疗效果方面具有巨大潜力。
