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

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.

Automated summary

Evidence suggests that prior antibiotic (pATB) administration may have a negative impact on the outcomes of PD-1 inhibitors in advanced gastric cancer (AGC) patients. pATB use is consistently associated with poorer progression-free survival (PFS) and overall survival (OS) in AGC patients treated with PD-1 inhibitors. pATB use is also linked to reduced gut microbiome diversity, decreased levels of beneficial bacteria Lactobacillus gasseri, and disproportionate enrichment of circulating exhaustive CD8+ T cells, all of which contribute to worse outcomes.