Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response
(1) Kim CG (2) Koh JY (3) Shin SJ (4) Shin JH (5) Hong M (6) Chung HC (7) Rha SY (8) Kim HS (9) Lee CK (10) Lee JH (11) Han Y (12) Kim H (13) Che X (14) Yun UJ (15) Kim H (16) Kim JH (17) Lee SY (18) Park SK (19) Park S (20) Kim H (21) Ahn JY (22) Jeung HC (23) Lee JS (24) Nam YD (25) Jung M
Kim, Koh, S-J Shin and J-H Shin et al. addressed the impact of prior antibiotic (pATB) administration in patients with advanced gastric cancer following PD-1 blockade. In multiple patient cohorts, pATB significantly decreased progression-free survival and overall survival, whereas outcomes in a patient cohort treated with chemotherapy (irinotecan) were unaffected by pATB administration. Mechanistically, pATBs significantly decreased gut microbiome diversity, reduced numbers of Lactobacillus gasseri, and disproportionately enriched circulating exhausted CD8+ T cells levels, all of which have been implicated in worse outcomes and decreased responses to PD-1 blockade.
Contributed by Katherine Turner
(1) Kim CG (2) Koh JY (3) Shin SJ (4) Shin JH (5) Hong M (6) Chung HC (7) Rha SY (8) Kim HS (9) Lee CK (10) Lee JH (11) Han Y (12) Kim H (13) Che X (14) Yun UJ (15) Kim H (16) Kim JH (17) Lee SY (18) Park SK (19) Park S (20) Kim H (21) Ahn JY (22) Jeung HC (23) Lee JS (24) Nam YD (25) Jung M
Kim, Koh, S-J Shin and J-H Shin et al. addressed the impact of prior antibiotic (pATB) administration in patients with advanced gastric cancer following PD-1 blockade. In multiple patient cohorts, pATB significantly decreased progression-free survival and overall survival, whereas outcomes in a patient cohort treated with chemotherapy (irinotecan) were unaffected by pATB administration. Mechanistically, pATBs significantly decreased gut microbiome diversity, reduced numbers of Lactobacillus gasseri, and disproportionately enriched circulating exhausted CD8+ T cells levels, all of which have been implicated in worse outcomes and decreased responses to PD-1 blockade.
Contributed by Katherine Turner
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.
Author Info:
(1) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (2) Graduate School of Med
ical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Genome Insight, Inc., Daejeon, Republic of Korea. (3) Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (4) Research Group of Personalized Diet, Korea Food Research Institute, Wanju, Republic of Korea. (5) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (6) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea. (7) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea. (8) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (9) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (10) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (11) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (12) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (13) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (14) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (15) Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (16) Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (17) Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (18) Deparment of Medical Records, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (19) Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea. (20) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. (21) Division of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. (22) Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jeunghc1123@yuhs.ac. (23) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Genome Insight, Inc., Daejeon, Republic of Korea. Electronic address: chemami@kaist.ac.kr. (24) Research Group of Personalized Diet, Korea Food Research Institute, Wanju, Republic of Korea. Electronic address: youngdo98@krfi.re.kr. (25) Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: minkjung@yuhs.ac.
Citation: Cell Rep Med 2023 Oct 25 101251 Epub10/25/2023
