Higher TIGIT expression in the intraperitoneal immune microenvironment is associated with shorter progression-free survival in patients with gastric cancer with peritoneal metastasis treated with intraperitoneal paclitaxel.
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引用次数: 0
Abstract
Purpose: Gastric cancer with peritoneal metastasis has a poor prognosis. This exploratory study evaluated whether immune checkpoint molecules in the intraperitoneal immune microenvironment are associated with clinical outcomes during intraperitoneal paclitaxel (ipPTX)-based combination chemotherapy.
Methods: Twenty-nine previously untreated patients with gastric cancer and macroscopic peritoneal metastasis who underwent staging laparoscopy and received ipPTX-based combination chemotherapy were retrospectively analyzed. Lymphocyte subsets in peritoneal lavage fluid were evaluated by flow cytometry. TIGIT, TIM-3, and LAG-3 expression was assessed in cell block specimens prepared from peritoneal lavage fluid by immunohistochemistry. Biomarker analyses were exploratory. Immune-related markers were analyzed primarily as continuous variables, and multivariable progression-free survival (PFS) and overall survival (OS) models were restricted to TIGIT and baseline Peritoneal Carcinomatosis Index (PCI) using Firth's penalized Cox regression.
Results: Median PFS and OS were 10.6 and 17.2 months, respectively. Among 27 patients evaluable for TIGIT, higher TIGIT expression was associated with shorter PFS in a continuous-variable Cox model (hazard ratio [HR] per 10-percentage-point increase, 1.53; 95% confidence interval [CI] 1.12-2.08; p = 0.008). After adjustment for baseline PCI, the association remained (HR, 1.48; 95% CI 1.04-2.10; p =0.030). TIM-3 did not show a clear association with survival outcomes.
Conclusions: Higher TIGIT expression in the intraperitoneal immune microenvironment was associated with shorter PFS in this small exploratory cohort receiving ipPTX-based combination chemotherapy.
目的：胃癌伴腹膜转移预后较差。本探索性研究评估了腹腔免疫微环境中的免疫检查点分子是否与腹腔紫杉醇（ipPTX）联合化疗期间的临床结果相关。方法：回顾性分析29例术前未经治疗的胃癌伴肉眼腹膜转移患者，经分期腹腔镜检查并以ipptx为基础联合化疗。用流式细胞术测定腹腔灌洗液淋巴细胞亚群。采用免疫组织化学方法检测腹腔灌洗液细胞块标本中TIGIT、TIM-3和LAG-3的表达。生物标志物分析是探索性的。免疫相关标志物主要作为连续变量进行分析，多变量无进展生存期（PFS）和总生存期（OS）模型使用Firth的惩罚Cox回归限制为TIGIT和基线腹膜癌指数（PCI）。结果：中位PFS和OS分别为10.6和17.2个月。在27例可评估TIGIT的患者中，在连续变量Cox模型中，较高的TIGIT表达与较短的PFS相关（每增加10个百分点的风险比[HR]为1.53；95%可信区间[CI]为1.12-2.08;p = 0.008）。调整基线PCI后，相关性仍然存在（HR, 1.48; 95% CI 1.04-2.10; p =0.030）。TIM-3没有显示出与生存结果的明确关联。结论：在这个接受基于ipptx联合化疗的小型探索性队列中，腹腔免疫微环境中较高的TIGIT表达与较短的PFS相关。
期刊介绍：
Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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