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

[Author]
Chang Gon Kim ^1 13, June-Young Koh ^2 3 13, Su-Jin Shin ^4 13, Ji-Hee Shin ^5 13, Moonki Hong ¹, Hyun Cheol Chung ^1 6, Sun Young Rha ^1 6, Hyo Song Kim ¹, Choong-Kun Lee ¹, Ji Hyun Lee ^1 11, Yejeong Han ^1 12, Hyoyong Kim ¹, Xiumei Che ¹, Un-Jung Yun ¹, Hyunki Kim ⁷, Jee Hung Kim ⁸, Seo Young Lee ⁸, Su Kyoung Park ⁹, Sejung Park ⁶, Hyunwook Kim ¹, Jin Young Ahn ¹⁰, Hei-Cheul Jeung ⁸, Jeong Seok Lee ^2 3, Young-Do Nam ⁵, Minkyu Jung ^1 6 14

¹Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea

²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea

³Genome Insight, Inc., Daejeon, Republic of Korea

⁴Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

⁵Research Group of Personalized Diet, Korea Food Research Institute, Wanju, Republic of Korea

⁶Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea

⁷Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

⁸Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

⁹Deparment of Medical Records, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

¹⁰Division of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

[Journal] 

Cell Reports Medicine Volume 4, Issue 11, 21 November 2023, 101251

[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.