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A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2

Testicular germ cell cancer (TGCC) is the most common type of cancer in young men. Seminomas account for around half of them and are characterized by a pronounced infiltration of immune cells. So far, the impact of the tumor microenvironment (TME) on disease progression, especially the interaction o...

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Autores principales: Gayer, Fabian A., Fichtner, Alexander, Legler, Tobias J., Reichardt, Holger M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909655/
https://www.ncbi.nlm.nih.gov/pubmed/35269507
http://dx.doi.org/10.3390/cells11050885
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author Gayer, Fabian A.
Fichtner, Alexander
Legler, Tobias J.
Reichardt, Holger M.
author_facet Gayer, Fabian A.
Fichtner, Alexander
Legler, Tobias J.
Reichardt, Holger M.
author_sort Gayer, Fabian A.
collection PubMed
description Testicular germ cell cancer (TGCC) is the most common type of cancer in young men. Seminomas account for around half of them and are characterized by a pronounced infiltration of immune cells. So far, the impact of the tumor microenvironment (TME) on disease progression, especially the interaction of individual immune cell subtypes with the tumor cells, remains unclear. To address this question, we used an in vitro TME model involving the seminoma-derived cell line Tcam-2 and immune cell subsets purified from human peripheral blood. T cells and monocytes were strongly activated when individually cocultured with Tcam-2 cells as revealed by increased expression of activation markers and pro-inflammatory cytokines both on the mRNA and protein level. Importantly, the interaction between tumor and immune cells was mutual. Gene expression of pluripotency markers as well as markers of proliferation and cell cycle activity were upregulated in Tcam-2 cells in cocultures with T cells, whereas gene expression of SOX17, a marker for seminomas, was unaltered. Interestingly, the impact of monocytes on gene expression of Tcam-2 cells was less pronounced, indicating that the effects of individual immune cell subsets on tumor cells in the TME are highly specific. Collectively, our data indicate that seminoma cells induce immune cell activation and thereby generate a strong pro-inflammatory milieu, whereas T cells conversely increase the proliferation, metastatic potential, and stemness of tumor cells. Although the employed model does not fully mimic the physiological situation found in TGCC in vivo, it provides new insights potentially explaining the connection between inflammatory infiltrates in seminomas and their tendency to burn out and metastasize.
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spelling pubmed-89096552022-03-11 A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2 Gayer, Fabian A. Fichtner, Alexander Legler, Tobias J. Reichardt, Holger M. Cells Article Testicular germ cell cancer (TGCC) is the most common type of cancer in young men. Seminomas account for around half of them and are characterized by a pronounced infiltration of immune cells. So far, the impact of the tumor microenvironment (TME) on disease progression, especially the interaction of individual immune cell subtypes with the tumor cells, remains unclear. To address this question, we used an in vitro TME model involving the seminoma-derived cell line Tcam-2 and immune cell subsets purified from human peripheral blood. T cells and monocytes were strongly activated when individually cocultured with Tcam-2 cells as revealed by increased expression of activation markers and pro-inflammatory cytokines both on the mRNA and protein level. Importantly, the interaction between tumor and immune cells was mutual. Gene expression of pluripotency markers as well as markers of proliferation and cell cycle activity were upregulated in Tcam-2 cells in cocultures with T cells, whereas gene expression of SOX17, a marker for seminomas, was unaltered. Interestingly, the impact of monocytes on gene expression of Tcam-2 cells was less pronounced, indicating that the effects of individual immune cell subsets on tumor cells in the TME are highly specific. Collectively, our data indicate that seminoma cells induce immune cell activation and thereby generate a strong pro-inflammatory milieu, whereas T cells conversely increase the proliferation, metastatic potential, and stemness of tumor cells. Although the employed model does not fully mimic the physiological situation found in TGCC in vivo, it provides new insights potentially explaining the connection between inflammatory infiltrates in seminomas and their tendency to burn out and metastasize. MDPI 2022-03-04 /pmc/articles/PMC8909655/ /pubmed/35269507 http://dx.doi.org/10.3390/cells11050885 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gayer, Fabian A.
Fichtner, Alexander
Legler, Tobias J.
Reichardt, Holger M.
A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title_full A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title_fullStr A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title_full_unstemmed A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title_short A Coculture Model Mimicking the Tumor Microenvironment Unveils Mutual Interactions between Immune Cell Subtypes and the Human Seminoma Cell Line TCam-2
title_sort coculture model mimicking the tumor microenvironment unveils mutual interactions between immune cell subtypes and the human seminoma cell line tcam-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909655/
https://www.ncbi.nlm.nih.gov/pubmed/35269507
http://dx.doi.org/10.3390/cells11050885
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