Kim Chan Yeong, Park Dong Jin, Ahn Beung Chul, Baek Seungbyn, Hong Min Hee, Nguyen Linh Thanh, Hwang Sun Ha, Kim Nayeon, Podlesny Daniel, Orakov Askarbek, Schudoma Christian, Robbani Shahriyar Mahdi, Shim Hyo Sup, Yoon Hong In, Lee Chang Young, Park Seong Yong, Yong Dongeun, Han Mina, Bork Peer, Kim Byoung Choul, Ha Sang-Jun, Kim Hye Ryun, Lee Insuk
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University, Seoul, 03722, Republic of Korea.
Nat Commun. 2024 Dec 27;15(1):10726. doi: 10.1038/s41467-024-55388-3.
Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions. However, gut microbiome biomarkers for ICB response have been inconsistent across different studies. Here, we identify TANB77, an uncultured and distinct bacterial clade, as the most consistent responder-enriched taxon through meta-analysis of ten independent ICB recipient cohorts. Traditional taxonomy fails to distinguish TANB77 from unrelated taxa, leading to its oversight. Mice with higher gut TANB77 abundance, either naturally or through transplantation, show improved response to anti-PD-1 therapy. Additionally, mice injected with TANB77-derived pilin-like protein exhibit improved anti-PD-1 therapy response, providing in vivo evidence for the beneficial role of the pilin-like protein. These findings suggest that pilins from the TANB77 order may enhance responses to ICB therapy across diverse cohorts of cancer patients.
免疫检查点阻断（ICB）已成为一种标准的抗癌治疗方法，可带来持久的临床益处。然而，ICB有限的响应率需要生物标志物来预测和调节治疗效果。肠道微生物群对ICB疗效的影响因其可通过各种干预措施进行调节而备受关注。然而，不同研究中关于ICB反应的肠道微生物群生物标志物并不一致。在这里，通过对十个独立的ICB接受者队列进行荟萃分析，我们确定了TANB77，这是一个未培养的独特细菌进化枝，是最一致的富集于反应者的分类单元。传统分类法无法将TANB77与不相关的分类单元区分开来，导致其被忽视。肠道TANB77丰度较高的小鼠，无论是自然状态下还是通过移植，对抗PD-1治疗的反应都有所改善。此外，注射TANB77衍生的菌毛样蛋白的小鼠对抗PD-1治疗的反应也有所改善，为菌毛样蛋白的有益作用提供了体内证据。这些发现表明，来自TANB77菌毛可能增强不同癌症患者队列对ICB治疗的反应。
