双歧杆菌在黑色素瘤小鼠模型中影响溶瘤腺病毒的抗肿瘤效果。
Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma.
发表日期：2023 Oct 20
作者：
Lorella Tripodi, Sara Feola, Ilaria Granata, Thomas Whalley, Margherita Passariello, Cristian Capasso, Ludovica Coluccino, Maria Vitale, Giulia Scalia, Laura Gentile, Claudia De Lorenzo, Mario Rosario Guarracino, Giuseppe Castaldo, Valeria D'Argenio, Barbara Szomolay, Vincenzo Cerullo, Lucio Pastore
来源：
Cell Death & Disease
摘要：
肠道微生物群对黑素瘤患者在肿瘤免疫治疗中的反应起着关键的调控作用。溶瘤病毒（OVs）是癌症治疗中新兴的工具，可以诱导免疫原性肿瘤细胞死亡（ICD）并招募免疫细胞进入T细胞浸润较差的肿瘤中。我们在小鼠黑素瘤的同种移植模型中研究了溶瘤腺病毒Ad5D24-CpG（Ad-CpG）的抗肿瘤活性是否受肠道微生物群调节，并观察到万古霉素干扰肠道微生物群导致ICD减弱。通过口服双歧杆菌对Ad-CpG进行补充，可以增加其疗效，减轻黑素瘤进展并减少肿瘤浸润的调节性T细胞。粪便微生物群在同时接受双歧杆菌和Ad-CpG处理的小鼠中富集了属于厚壁菌门的细菌物种；此外，我们的数据表明，黑素瘤与双歧杆菌源性表位之间的分子拟态可能有利于交叉反应性T细胞的激活，并构成肠道微生物群调节OVs反应的机制之一。©2023 作者。
Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response.© 2023 The Authors.