A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy
  • Kim, Chan Yeong
  • Park, Dong Jin
  • Ahn, Beung Chul
  • Baek, Seungbyn
  • Hong, Min Hee
  • ... Park, Seong Yong
  • 외 17명
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초록

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.

키워드

DATABASEGENOMESEQUENCESTHERAPYPEMBROLIZUMABMICROBIOMEANNOTATIONASSIGNMENTALIGNMENTBLOCKADE
제목
A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy
저자
Kim, Chan YeongPark, Dong JinAhn, Beung ChulBaek, SeungbynHong, Min HeeNguyen, Linh ThanhHwang, Sun HaKim, NayeonPodlesny, DanielOrakov, AskarbekSchudoma, ChristianRobbani, Shahriyar MahdiShim, Hyo SupYoon, Hong InLee, Chang YoungPark, Seong YongYong, DongeunHan, MinaBork, PeerKim, Byoung ChoulHa, Sang-JunKim, Hye RyunLee, Insuk
DOI
10.1038/s41467-024-55388-3
발행일
2024-12
유형
Article
저널명
Nature Communications
15
1