Improved survival by Helicobacter pylori-modulated immunity in gastric cancer patients with S-1 adjuvant chemotherapy
Improved survival by Helicobacter pylori-modulated immunity in gastric cancer patients with S-1 adjuvant chemotherapy
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DOI：
10.1101/2021.09.24.21263620
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发表时间：
2021-09
期刊：
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通讯作者：
Y. Koizumi;S. Ahmad;M. Ikeda;A. Yashima‐Abo;G. Espina;R. Sugimoto;T. Sugai;T. Iwaya;K. Koeda;L. Liotta;F. Takahashi;S. Nishizuka
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作者：
Y. Koizumi;S. Ahmad;M. Ikeda;A. Yashima‐Abo;G. Espina;R. Sugimoto;T. Sugai;T. Iwaya;K. Koeda;L. Liotta;F. Takahashi;S. Nishizuka
背景资料：幽门螺杆菌阳性（HP+）的进展期胃癌患者的预后比HP阴性（HP-）的患者更好。免疫学和统计学分析可用于验证HP调节的系统机制是否参与了这种更有利的结果。方法：658例进展期胃癌患者行全胃切除术。分析HP感染、错配修复、程序性死亡配体1（PD-L1）和CD 4/CD 8蛋白以及微卫星不稳定性。对临床病理因素进行分层后，分析总生存率（OS）和无复发生存率（RFS）。考克斯比例风险回归分析，以确定独立的预后因素。结果：491例患者中，HP阳性175例（36%），HP阴性316例（64%）。RFS分析表明，S-1剂量（P=0.0487）和PD-L1（P=0.016）亚组之间HP状态存在相互作用。PD-L1组HP+患者的5年OS和RFS显著高于HP-患者（分别为81% vs. 68%; P=0.0011; HR 0.477;和76% vs. 63%; P=0.0011; HR 0.508）。在PD-L1/S-1降低组中，HP患者的5年OS和RFS也显著高于HP患者（分别为86% vs. 46%; p=0.0014; HR 0.205; 83% vs. 34%; p=0.001; HR 0.190）。因此，HP状态被确定为预测生存期延长的最重要的潜在独立因素之一。结论：HP对宿主免疫系统功能的调节可能有助于在缺乏胃癌免疫逃逸机制的情况下延长生存期。
Background: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systematic mechanisms modulated by HP are involved in this more favorable outcome. Methods: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 Dose (P=0.0487) and PD-L1 (P=0.016). HP+ patients in the PD-L1- group had significantly higher five-year OS and RFS than HP- patients (81% vs. 68%; P=0.0011; HR 0.477; and 76% vs. 63%; P=0.0011; HR 0.508, respectively). The five-year OS and RFS was also significantly higher for HP compared to HP- patients in the PD-L1-/S-1-reduced group (86% vs. 46%; p=0.0014; HR 0.205; 83% vs. 34%; p=0.001; HR 0.190, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. Conclusion: Modulation of host immune system function by HP may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.