Department of Women's Health Tübingen, University of Tübingen, Tübingen, Germany.
Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, University of Tübingen, Tübingen, Germany.
Front Immunol. 2024 Mar 5;15:1357340. doi: 10.3389/fimmu.2024.1357340. eCollection 2024.
In the context of multimodal treatments for abdominal cancer, including procedures such as cytoreductive surgery and intraperitoneal chemotherapy, recurrence rates remain high, and long-term survival benefits are uncertain due to post-operative complications. Notably, treatment-limiting side effects often arise from an uncontrolled activation of the immune system, particularly peritoneally localized macrophages, leading to massive cytokine secretion and phenotype changes. Exploring alternatives, an increasing number of studies investigated the potential of plasma-activated liquids (PAL) for adjuvant peritoneal cancer treatment, aiming to mitigate side effects, preserve healthy tissue, and reduce cytotoxicity towards non-cancer cells. To assess the non-toxicity of PAL, we isolated primary human macrophages from the peritoneum and subjected them to PAL exposure. Employing an extensive methodological spectrum, including flow cytometry, Raman microspectroscopy, and DigiWest protein analysis, we observed a pronounced resistance of macrophages towards PAL. This resistance was characterized by an upregulation of proliferation and anti-oxidative pathways, countering PAL-derived oxidative stress-induced cell death. The observed cellular effects of PAL treatment on human tissue-resident peritoneal macrophages unveil a potential avenue for PAL-derived immunomodulatory effects within the human peritoneal cavity. Our findings contribute to understanding the intricate interplay between PAL and macrophages, shedding light on the promising prospects for PAL in the adjuvant treatment of peritoneal cancer.
在包括细胞减灭术和腹腔内化疗在内的腹部癌症多模态治疗中,复发率仍然很高,由于术后并发症,长期生存获益不确定。值得注意的是,治疗限制的副作用通常是由于免疫系统的失控激活引起的,特别是腹膜局部巨噬细胞,导致大量细胞因子分泌和表型改变。为了探索替代方法,越来越多的研究调查了等离子体激活液(PAL)在辅助腹膜癌治疗中的潜力,旨在减轻副作用、保护健康组织和降低对非癌细胞的细胞毒性。为了评估 PAL 的非毒性,我们从腹膜中分离出原代人巨噬细胞并使其暴露于 PAL 下。采用广泛的方法学谱,包括流式细胞术、拉曼微光谱和 DigiWest 蛋白分析,我们观察到巨噬细胞对 PAL 具有明显的抗性。这种抗性的特征是增殖和抗氧化途径的上调,对抗 PAL 衍生的氧化应激诱导的细胞死亡。PAL 处理对人组织驻留腹膜巨噬细胞的观察到的细胞效应揭示了 PAL 衍生的免疫调节效应在人类腹膜腔中的潜在途径。我们的研究结果有助于理解 PAL 和巨噬细胞之间的复杂相互作用,为 PAL 在腹膜癌辅助治疗中的应用前景提供了新的思路。