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描述腹膜癌转移中的免疫环境:对新型免疫治疗策略的启示。

Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies.

机构信息

Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA.

Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Ann Surg Oncol. 2024 Mar;31(3):2069-2077. doi: 10.1245/s10434-023-14553-6. Epub 2023 Nov 23.

Abstract

BACKGROUND OR PURPOSE

Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies.

PATIENTS AND METHODS

Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples.

RESULTS

There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid.

CONCLUSIONS

The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.

摘要

背景或目的

癌性腹水是一种独特的腹腔转移癌模式,给治疗带来了挑战,且治疗选择有限。了解腹膜表面恶性肿瘤的免疫环境对于开发有效的免疫治疗方法至关重要。本研究旨在分析有/无癌性腹水患者的腹腔液中可溶性免疫介质,以确定新的治疗策略的靶点。

患者和方法

收集手术患者的血清和腹腔液样本,并使用 Luminex 平台进行多分析物分析。记录患者特征、肿瘤部位和样本采集细节。测量并比较了腹腔液和血清样本以及临床亚组之间可溶性免疫介质的水平。进行了统计分析,以评估分析物浓度的差异以及样本之间的相关性。

结果

本研究共纳入 39 例患者,手术指征各不相同。腹腔液和血清中的可溶性免疫介质水平存在显著差异,腹腔液中的浓度较低。癌性腹水与促炎介质(如 IL-6 和 IL-8)水平升高有关,而适应性免疫反应标志物在腹腔液中水平较低。

结论

癌性腹水的腹膜免疫微环境有利于固有免疫,为有效的抗肿瘤反应创造了具有挑战性的环境。促炎介质水平升高提示潜在的干预靶点,如 IL-6 轴、FGF2、IL-8 和 CCL2;这些靶点可作为治疗恶性腹水和增强抗肿瘤免疫反应的潜在药物。这些发现为开发免疫治疗策略和改善腹膜癌性腹水患者的预后提供了有价值的信息。

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