정민규 (연세대학교 의과대학)

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연세대학교 의과대학

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Cell Rep. Med., October 26, 2023 | https://doi.org/10.1016/j.xcrm.2023.101251 Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response

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,* and 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
¹¹Present address: Division of Medical Oncology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
¹²Present address: Department of Hematology-Oncology, Inha University College of Medicine, Incheon, Republic of Korea
¹³These authors contributed equally
¹⁴Lead contact

^*Corresponding authors: correspondence to Hei-Cheul Jeung, Jeong Seok Lee, Young-Do Nam or Minkyu Jung

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.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-27)
연구진국내 연구진
분야 의약학 > 응용의학

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