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CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients
We investigated the mechanisms affecting tumor progression and survival outcomes in Polybromo-1-mutated (PBRM1(MUT)) clear cell renal cell carcinoma (ccRCC) patients. PBRM1(MUT) ccRCC tissues contained higher numbers of mast cells and lower numbers of CD8(+) and CD4(+) T cells than tissues from PBRM...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695370/ https://www.ncbi.nlm.nih.gov/pubmed/33177244 http://dx.doi.org/10.18632/aging.103999 |
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author | Liu, Tianjie Xia, Qing Zhang, Haibao Wang, Zixi Yang, Wenjie Gu, Xiaoyun Hou, Tao Chen, Yule Pei, Xinqi Zhu, Guodong He, Dalin Li, Lei Xu, Shan |
author_facet | Liu, Tianjie Xia, Qing Zhang, Haibao Wang, Zixi Yang, Wenjie Gu, Xiaoyun Hou, Tao Chen, Yule Pei, Xinqi Zhu, Guodong He, Dalin Li, Lei Xu, Shan |
author_sort | Liu, Tianjie |
collection | PubMed |
description | We investigated the mechanisms affecting tumor progression and survival outcomes in Polybromo-1-mutated (PBRM1(MUT)) clear cell renal cell carcinoma (ccRCC) patients. PBRM1(MUT) ccRCC tissues contained higher numbers of mast cells and lower numbers of CD8(+) and CD4(+) T cells than tissues from PBRM1(WT) ccRCC patients. Hierarchical clustering, pathway enrichment and GSEA analyses demonstrated that PBRM1 mutations promote tumor progression by activating hypoxia inducible factor (HIF)-related signaling pathways and increasing expression of vascular endothelial growth factor family genes. PBRM1(MUT) ccRCC tissues also show increased expression of C-C motif chemokine ligand 5 (CCL5). PBRM1-silenced ccRCC cells exhibited greater Matrigel tube formation and cell proliferation than controls. In addition, HMC-1 human mast cells exhibited CCL5-dependent in vitro migration on Transwell plates. High CCL5 expression in PBRM1(MUT) ccRCC patients correlated with increased expression of genes encoding IFN-γ, IFN-α, IL-6, JAK-STAT3, TNF-α, and NF-ΚB. Moreover, high CCL5 expression was associated with poorer survival outcomes in ccRCC patients. These findings demonstrate that CCL5-dependent mast cell infiltration promotes immunosuppression within the tumor microenvironment, resulting in tumor progression and adverse survival outcomes in PBRM1(MUT) ccRCC patients. |
format | Online Article Text |
id | pubmed-7695370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-76953702020-12-04 CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients Liu, Tianjie Xia, Qing Zhang, Haibao Wang, Zixi Yang, Wenjie Gu, Xiaoyun Hou, Tao Chen, Yule Pei, Xinqi Zhu, Guodong He, Dalin Li, Lei Xu, Shan Aging (Albany NY) Research Paper We investigated the mechanisms affecting tumor progression and survival outcomes in Polybromo-1-mutated (PBRM1(MUT)) clear cell renal cell carcinoma (ccRCC) patients. PBRM1(MUT) ccRCC tissues contained higher numbers of mast cells and lower numbers of CD8(+) and CD4(+) T cells than tissues from PBRM1(WT) ccRCC patients. Hierarchical clustering, pathway enrichment and GSEA analyses demonstrated that PBRM1 mutations promote tumor progression by activating hypoxia inducible factor (HIF)-related signaling pathways and increasing expression of vascular endothelial growth factor family genes. PBRM1(MUT) ccRCC tissues also show increased expression of C-C motif chemokine ligand 5 (CCL5). PBRM1-silenced ccRCC cells exhibited greater Matrigel tube formation and cell proliferation than controls. In addition, HMC-1 human mast cells exhibited CCL5-dependent in vitro migration on Transwell plates. High CCL5 expression in PBRM1(MUT) ccRCC patients correlated with increased expression of genes encoding IFN-γ, IFN-α, IL-6, JAK-STAT3, TNF-α, and NF-ΚB. Moreover, high CCL5 expression was associated with poorer survival outcomes in ccRCC patients. These findings demonstrate that CCL5-dependent mast cell infiltration promotes immunosuppression within the tumor microenvironment, resulting in tumor progression and adverse survival outcomes in PBRM1(MUT) ccRCC patients. Impact Journals 2020-11-11 /pmc/articles/PMC7695370/ /pubmed/33177244 http://dx.doi.org/10.18632/aging.103999 Text en Copyright: © 2020 Liu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Tianjie Xia, Qing Zhang, Haibao Wang, Zixi Yang, Wenjie Gu, Xiaoyun Hou, Tao Chen, Yule Pei, Xinqi Zhu, Guodong He, Dalin Li, Lei Xu, Shan CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title | CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title_full | CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title_fullStr | CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title_full_unstemmed | CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title_short | CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
title_sort | ccl5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695370/ https://www.ncbi.nlm.nih.gov/pubmed/33177244 http://dx.doi.org/10.18632/aging.103999 |
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