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Introduction <p>Immune checkpoint inhibitors (ICIs) are essential for treating esophageal squamous cell carcinoma (ESCC). As antibiotics (Abx) may reduce ICI efficacy, and immune-related adverse events (irAEs) relate to better outcomes, we investigated their association.</p> Patients and methods <p>We retrospectively analyzed 121 advanced or metastatic ESCC patients treated with ICIs, assessing outcomes based on Abx use and irAEs.</p> Results <p>Forty-one patients (33.9%) were in the Abx (+) group, showing a significantly shorter median progression-free survival (PFS) (2.5 vs. 6.5&#xa0;months; <i>p</i> = 0.029) and lower disease control rate (36.8% vs. 60.9%; <i>p</i> = 0.0145) than those in the Abx (−) group. irAEs were less frequent in the Abx (+) group (29.3% vs. 58.8%; <i>p</i> = 0.0037). The positive impact of irAEs on ICI efficacy was significant in overall population [irAE(−) vs. irAE(+): PFS, 4.4&#xa0;months (95% CI 2.5–5.3) vs. 8.8&#xa0;months (95% CI 5.9–13.7); log-rank <i>p</i> = 0.001; Hazard ratio (HR) 1.76, 95% CI 1.14–2.74; <i>p</i> = 0.011; overall survival (OS), 10.6&#xa0;months (95% CI 7.0–13.1) vs. 18.1&#xa0;months (95% CI 9.2–25.9); log-rank<i> p</i> = 0.043; HR 1.61, 95% CI 1.01–2.55; <i>p</i> = 0.046] but diminished if received Abx. Notably, the Abx (−)/irAE (+) group had the best outcomes, while the Abx (+)/irAE (−) group had the worst PFS (8.7 vs. 2.4&#xa0;months; HR 2.07; <i>p</i> = 0.011) and OS (18.1 and 6.8&#xa0;months; HR 1.89; <i>p</i> = 0.036).</p> Conclusion <p>Antibiotic use was linked to reduced ICI efficacy and fewer irAEs, suggesting impaired immune activation in ESCC patients.</p>

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Association between antibiotic use, immune-related adverse events, and efficacy of immunotherapy in esophageal squamous cell carcinoma

  • 期刊论文

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  • 发表日期：

    2026年4月27日

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  • Tomoaki Shirakawa,
  • Hiroo Imai,
  • Ken Saijo,
  • Ryo Saito,
  • Shiori Ishikawa,
  • Iori Takahashi,
  • Keigo Komine,
  • Kota Ouchi,
  • Yuki Kasahara,
  • Sakura Taniguchi,
  • Yuya Yoshida,
  • Ryunosuke Numakura,
  • Shonosuke Wakayama,
  • Hidekazu Shirota,
  • Masanobu Takahashi,
  • Hisato Kawakami

摘要

Introduction

Immune checkpoint inhibitors (ICIs) are essential for treating esophageal squamous cell carcinoma (ESCC). As antibiotics (Abx) may reduce ICI efficacy, and immune-related adverse events (irAEs) relate to better outcomes, we investigated their association.

Patients and methods

We retrospectively analyzed 121 advanced or metastatic ESCC patients treated with ICIs, assessing outcomes based on Abx use and irAEs.

Results

Forty-one patients (33.9%) were in the Abx (+) group, showing a significantly shorter median progression-free survival (PFS) (2.5 vs. 6.5 months; p = 0.029) and lower disease control rate (36.8% vs. 60.9%; p = 0.0145) than those in the Abx (−) group. irAEs were less frequent in the Abx (+) group (29.3% vs. 58.8%; p = 0.0037). The positive impact of irAEs on ICI efficacy was significant in overall population [irAE(−) vs. irAE(+): PFS, 4.4 months (95% CI 2.5–5.3) vs. 8.8 months (95% CI 5.9–13.7); log-rank p = 0.001; Hazard ratio (HR) 1.76, 95% CI 1.14–2.74; p = 0.011; overall survival (OS), 10.6 months (95% CI 7.0–13.1) vs. 18.1 months (95% CI 9.2–25.9); log-rank p = 0.043; HR 1.61, 95% CI 1.01–2.55; p = 0.046] but diminished if received Abx. Notably, the Abx (−)/irAE (+) group had the best outcomes, while the Abx (+)/irAE (−) group had the worst PFS (8.7 vs. 2.4 months; HR 2.07; p = 0.011) and OS (18.1 and 6.8 months; HR 1.89; p = 0.036).

Conclusion

Antibiotic use was linked to reduced ICI efficacy and fewer irAEs, suggesting impaired immune activation in ESCC patients.