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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
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
Descripción
Sumario: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.