Weill Cornell Medical College, New York, New York, USA.
Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
J Immunother Cancer. 2023 Oct;11(10). doi: 10.1136/jitc-2023-007699.
Gut microbiota composition can influence cancer immunotherapy response. Recent evidence suggests infection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact of on survival in this population.
This single-center, retrospective study included all ICI-treated individuals with metastatic gastric cancer and documented status at Memorial Sloan Kettering between July 2013 and October 2021. -positive status was defined as history of infection obtained via breath test, stool antigen test, histopathology, and/or chart documentation. Negative status was defined as explicitly negative testing, histopathology, and/or chart documentation. Primary outcomes were progression-free survival (PFS) and overall survival (OS).
Of 215 included patients, 49 had documented history of infection. Compared with negative patients, positive individuals tended to be younger, non-white, and Hispanic with non-cardia and intestinal-type gastric cancer. positive patients had significantly shorter median PFS (3.2 vs 6.8 months, HR 1.96, p<0.01) and OS (9.8 vs 17.9 months, HR 1.54, p=0.02). Multivariable analysis confirmed infection as an independent predictor of PFS (HR 3.04, p<0.01) and OS (HR 2.24, p=0.01).
In this largest study of its kind, infection was associated with inferior survival in ICI-treated patients with gastric cancer. This suggests status may be a prognostic marker of immune responsiveness. Future studies are needed to elucidate immunoregulatory mechanisms and whether treatment of active infections would improve immunotherapy outcomes.
肠道微生物组成可以影响癌症免疫治疗的反应。最近的证据表明，感染可能会降低肺癌和黑色素瘤中免疫检查点抑制剂（ICI）的疗效，但在胃癌患者中对这种关联的全面描述还很缺乏。我们旨在确定这种在该人群中的感染对生存的影响。
这项单中心、回顾性研究包括 2013 年 7 月至 2021 年 10 月期间在纪念斯隆凯特琳癌症中心接受 ICI 治疗的所有转移性胃癌患者，并记录了他们的感染状况。阳性状态定义为通过呼气试验、粪便抗原试验、组织病理学和/或病历记录获得的感染史。阴性状态定义为明确的阴性检测、组织病理学和/或病历记录。主要结局是无进展生存期（PFS）和总生存期（OS）。
在 215 名纳入的患者中，有 49 名有记录的感染史。与阴性患者相比，阳性患者年龄较小，为非裔或拉丁裔，非贲门和肠型胃癌。阳性患者的中位 PFS（3.2 个月比 6.8 个月，HR 1.96，p<0.01）和 OS（9.8 个月比 17.9 个月，HR 1.54，p=0.02）显著更短。多变量分析证实感染是 PFS（HR 3.04，p<0.01）和 OS（HR 2.24，p=0.01）的独立预测因素。
在这项最大规模的同类研究中，感染与接受 ICI 治疗的胃癌患者的生存不良相关。这表明感染状态可能是免疫反应性的预后标志物。需要进一步研究阐明免疫调节机制，以及是否治疗活动性感染会改善免疫治疗效果。
