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Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response

Authors
 Chang Gon Kim  ;  June-Young Koh  ;  Su-Jin Shin  ;  Ji-Hee Shin  ;  Moonki Hong  ;  Hyun Cheol Chung  ;  Sun Young Rha  ;  Hyo Song Kim  ;  Choong-Kun Lee  ;  Ji Hyun Lee  ;  Yejeong Han  ;  Hyoyong Kim  ;  Xiumei Che  ;  Un-Jung Yun  ;  Hyunki Kim  ;  Jee Hung Kim  ;  Seo Young Lee  ;  Su Kyoung Park  ;  Sejung Park  ;  Hyunwook Kim  ;  Jin Young Ahn  ;  Hei-Cheul Jeung  ;  Jeong Seok Lee  ;  Young-Do Nam  ;  Minkyu Jung 
Citation
 CELL REPORTS MEDICINE, Vol.4(11) : 101251, 2023-11 
Journal Title
CELL REPORTS MEDICINE
Issue Date
2023-11
MeSH
Anti-Bacterial Agents ; CD8-Positive T-Lymphocytes ; Gastrointestinal Microbiome* ; Humans ; Immune Checkpoint Inhibitors / therapeutic use ; Programmed Cell Death 1 Receptor ; Stomach Neoplasms* / drug therapy
Keywords
PD-1 inhibitor ; advanced gastric cancer ; antibiotics ; chemotherapy ; gut microbiome ; systemic immune response
Abstract
Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.
Files in This Item:
T202306709.pdf Download
DOI
10.1016/j.xcrm.2023.101251
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jee Hung(김지형) ORCID logo https://orcid.org/0000-0002-9044-8540
Kim, Chang Gon(김창곤)
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hyun Wook(김현욱) ORCID logo https://orcid.org/0000-0002-4274-7562
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Ahn, Jin Young(안진영) ORCID logo https://orcid.org/0000-0002-3740-2826
Yun, Un-Jung(윤언정)
Lee, Seoyoung(이서영)
Lee, Ji Hyun(이지현)
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
Hong, Moonki(홍문기) ORCID logo https://orcid.org/0000-0001-9528-4912
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197272
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