A myeloid and lymphoid infiltrate in murine pancreatic tumors exposed to plasma-treated medium

Q1 Medicine Clinical Plasma Medicine Pub Date : 2018-09-01 DOI:10.1016/j.cpme.2018.07.001
Kim Rouven Liedtke , Eric Freund , Christine Hackbarth , Claus-Dieter Heidecke , Lars-Ivo Partecke , Sander Bekeschus
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引用次数: 36

Abstract

Purpose

Metastatic pancreatic cancer often is fatal in patients. Palliation can include disseminating large amounts of chemotherapeutic liquid in the peritoneal cavity to slow tumor growth. We have previously demonstrated that repeated application of plasma-treated medium performed well in decreasing peritoneal tumor burden in mice and prolonging animal survival. We here extend on this study by detailed immune-related analysis of cryo-conserved tumor nodes of mice that had received either cell culture medium alone or plasma-treated cell culture medium.

Methods

Animals of the treatment group had significantly fewer lesions, which were characterized by an in-creased influx of macrophages. The staining intensity of CD206, a murine M2 macrophage marker associated with tumor promotion, was decreased in tissue sections, while iNOS (M1 marker associated with inflammatory macrophages) was not changed. In the infiltrate, other myeloid cells such as neutrophils and dendritic cells were in tendency increased and decreased, respectively. Further, we observed a significant increase in T cells and calreticulin staining, suggesting an involvement of immunogenic cancer cell death in plasma-treated medium therapy of pancreatic tumor lesions.

Conclusion

In summary, exposure to plasma-treated medium not only decelerates tumor growth but also serves as immunomodulatory agent with a possible relevance for therapeutic outcome.

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暴露于血浆处理的小鼠胰腺肿瘤中的骨髓和淋巴浸润
目的转移性胰腺癌往往是致命的。姑息包括在腹腔内播散大量的化疗液体以减缓肿瘤的生长。我们之前已经证明反复应用等离子处理的培养基可以很好地减少小鼠腹膜肿瘤负荷并延长动物生存期。我们在此扩展了这项研究,通过对单独接受细胞培养基或接受等离子处理细胞培养基的小鼠冷冻保存的肿瘤淋巴结进行详细的免疫相关分析。方法治疗组动物病变明显减少,其特征是巨噬细胞内流增加。组织切片中与肿瘤促进相关的M2巨噬细胞标志物CD206的染色强度降低,而与炎性巨噬细胞相关的M1标志物iNOS未发生变化。在浸润中,其他髓系细胞如中性粒细胞和树突状细胞分别有增加和减少的趋势。此外,我们观察到T细胞和钙调蛋白染色显著增加,表明免疫原性癌细胞死亡参与了血浆治疗胰腺肿瘤病变的培养基治疗。综上所述,暴露于血浆处理的培养基中不仅可以减缓肿瘤的生长,而且还可以作为免疫调节剂,可能与治疗结果有关。
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Clinical Plasma Medicine
Clinical Plasma Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
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