Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentra...

Full description

Bibliographic Details
Main Authors: Katrin Rödder, Juliane Moritz, Vandana Miller, Klaus-Dieter Weltmann, Hans-Robert Metelmann, Rajesh Gandhirajan, Sander Bekeschus
Format: Article
Language:English
Published: MDPI AG 2019-02-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/9/4/660
_version_ 1818152500099809280
author Katrin Rödder
Juliane Moritz
Vandana Miller
Klaus-Dieter Weltmann
Hans-Robert Metelmann
Rajesh Gandhirajan
Sander Bekeschus
author_facet Katrin Rödder
Juliane Moritz
Vandana Miller
Klaus-Dieter Weltmann
Hans-Robert Metelmann
Rajesh Gandhirajan
Sander Bekeschus
author_sort Katrin Rödder
collection DOAJ
description Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells’ activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone.
first_indexed 2024-12-11T13:55:42Z
format Article
id doaj.art-a7f627e9dc574391957cf0c68dc81f25
institution Directory Open Access Journal
issn 2076-3417
language English
last_indexed 2024-12-11T13:55:42Z
publishDate 2019-02-01
publisher MDPI AG
record_format Article
series Applied Sciences
spelling doaj.art-a7f627e9dc574391957cf0c68dc81f252022-12-22T01:04:05ZengMDPI AGApplied Sciences2076-34172019-02-019466010.3390/app9040660app9040660Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma CellsKatrin Rödder0Juliane Moritz1Vandana Miller2Klaus-Dieter Weltmann3Hans-Robert Metelmann4Rajesh Gandhirajan5Sander Bekeschus6Centre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyCentre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyCentre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyCentre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyDepartment of Oral and Maxillofacial Surgery/Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str. DZ 7, 17475 Greifswald, GermanyCentre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyCentre for Innovation Competence (ZIK) <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str.2, 17489 Greifswald, GermanyRecent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells&#8217; activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1&#946; (IL-1&#946;) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone.https://www.mdpi.com/2076-3417/9/4/660kINPenlymphocytesmacrophagesplasma medicinereactive species
spellingShingle Katrin Rödder
Juliane Moritz
Vandana Miller
Klaus-Dieter Weltmann
Hans-Robert Metelmann
Rajesh Gandhirajan
Sander Bekeschus
Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
Applied Sciences
kINPen
lymphocytes
macrophages
plasma medicine
reactive species
title Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
title_full Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
title_fullStr Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
title_full_unstemmed Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
title_short Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells
title_sort activation of murine immune cells upon co culture with plasma treated b16f10 melanoma cells
topic kINPen
lymphocytes
macrophages
plasma medicine
reactive species
url https://www.mdpi.com/2076-3417/9/4/660
work_keys_str_mv AT katrinrodder activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT julianemoritz activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT vandanamiller activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT klausdieterweltmann activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT hansrobertmetelmann activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT rajeshgandhirajan activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells
AT sanderbekeschus activationofmurineimmunecellsuponcoculturewithplasmatreatedb16f10melanomacells