Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells

Abstract

Macrophages and immuno-modulation play a dominant role in the pathology of pancreatic cancer. Gas plasma is a technology recently suggested to demonstrate anticancer efficacy. To this end, two murine cell lines were employed to analyze the inflammatory consequences of plasma-treated pancreatic cancer cells (PDA) on macrophages using the kINPen plasma jet. Plasma treatment decreased the metabolic activity, viability, and migratory activity in an ROS- and treatment time-dependent manner in PDA cells in vitro. These results were confirmed in pancreatic tumors grown on chicken embryos in the TUM-CAM model (in ovo). PDA cells promote tumor-supporting M2 macrophage polarization and cluster formation. Plasma treatment of PDA cells abrogated this cluster formation with a mixed M1/M2 phenotype observed in such co-cultured macrophages. Multiplex chemokine and cytokine quantification showed a marked decrease of the neutrophil chemoattractant CXCL1, IL6, and the tumor growth supporting TGFβ and VEGF in plasma-treated compared to untreated co-culture settings. At the same time, macrophage-attractant CCL4 and MCP1 release were profoundly enhanced. These cellular and secretome data suggest that the plasma-inactivated PDA6606 cells modulate the inflammatory profile of murine RAW 264.7 macrophages favorably, which may support plasma cancer therapy.

Current State of Cold Atmospheric Plasma and Cancer‐Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels

“…Altered surface marker expression (Differentiation, maturation, and polarization ↑, pro-inflammatory phenotype tendency ↑) CC Direct: [ 117,57] (in vitro) Indirect: [49] (in vitro) [ 118,119,51] (in vivo) IC Direct: [ 109,113,115,118] (in vitro) Indirect: [ 110] (in vitro)…”

“…Altered secretory profile (Pro-inflammatory tendency ↑) CC Direct: [ 117,57] (in vitro), [ 55,59] (in vivo) Indirect: [49] (in vitro) IC Direct: [ 109,113,115,118,120,57] (in vitro) Indirect: [ 110] (in vitro)…”

Research Advances and Application Prospect of Low-Temperature Plasma in Tumor Immunotherapy

“…Miller et al [33] found that low-plasma-treated macrophages showed an increased migratory activity and mediated tumor cell killing in a TNF-α-mediated manner. Khabipov et al [34] studied plasma exposure of pancreatic ductal adenocarcinoma (PDA), and subsequent co-culture with macrophages significantly reduced the number of macrophage clusters compared to untreated PDA cells. Therefore, tumor therapy by targeting proinflammatory macrophages may become an attractive anti-tumor treatment strategy.…”

In ovo model in cancer research and tumor immunology

“…Several studies have further focused on metabolic profiling via mass spectrometry ( 33 , 34 ) or positron emission tomography (PET) imaging for evaluation of glucose metabolism and protein synthesis ( 53 ). At the simplest, the metabolic activity can be assessed by conventional colorimetric or fluorescence-based methods, including resazurin, MTT, and WST assays before or after tumor dissociation ( 10 ). While non-malignant cells exhibit a limited number of divisions, cancer cells bypass this barrier by hijacking telomerases to extend the length of their telomeres.…”