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Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment
BACKGROUND: Cellular heterogeneity within the tumor microenvironment is essential to tumorigenesis and tumor development. A high-resolution global view of the tumor-infiltrating immune and stromal cells in breast tumors is needed. METHODS: xCell was used to create a cellular heterogeneity map of 64...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357563/ https://www.ncbi.nlm.nih.gov/pubmed/32728493 http://dx.doi.org/10.7717/peerj.9478 |
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author | Li, Yuan Chen, Zuhua Wu, Long Ye, Junjie Tao, Weiping |
author_facet | Li, Yuan Chen, Zuhua Wu, Long Ye, Junjie Tao, Weiping |
author_sort | Li, Yuan |
collection | PubMed |
description | BACKGROUND: Cellular heterogeneity within the tumor microenvironment is essential to tumorigenesis and tumor development. A high-resolution global view of the tumor-infiltrating immune and stromal cells in breast tumors is needed. METHODS: xCell was used to create a cellular heterogeneity map of 64 cell types in 1,092 breast tumor and adjacent normal tissues. xCell digitally dissects tissue cellular heterogeneity based on gene expression. Integrated statistical analyses were then performed. RESULTS: There were noticeable differences between the cell fractions in tumor tissues and normal tissues. Tumors displayed higher proportions of immune cells, including CD4+ Tem, CD8+ naïve T cells, and CD8+ Tcm compared with normal tissues. Immune inhibitory receptors (PD1, CTLA4, LAG3 and TIM3) were co-expressed on certain subtypes of T cells in breast tumors, and PD1 and CTLA4 were both positively correlated with CD8+ Tcm and CD8+ T cells. 28 cell types were significantly associated with overall survival in univariate analysis. CD4+ Tem, CD8+ Tcm, CD8+ T-cells, CD8+ naive T-cells, and B cells were positive prognostic factors but CD4+ naive T-cells were negative prognostic factors for breast cancer patients. TDRD6 and TTK are promising T cell and B cell targets for tumor vaccines. Endothelial cells and fibroblasts were significantly less prevalent in tumor tissues; astrocytes and mesangial cells were negatively correlated with the T stage. Mesangial cells and keratinocytes were found to be favorable prognostic factors and myocytes were negative prognostic factors. Five cell types were found to be independent prognostic factors and we used these to create a reliable prognostic model for breast cancer patients. Cellular heterogeneity was discovered among different breast cancer subtypes by Her2, ER, and PR status. Tri-negative patients had the highest fraction of immune cells while luminal type patients had the lowest. The various cells may have diverse or opposing roles in the prognosis of breast cancer patients. CONCLUSIONS: We created a uniquecellular map for the diverse heterogeneity of immune and stromal phenotypes within the breast tumor microenvironment. This map may lead to potential therapeutic targets and biomarkers with prognostic utility. |
format | Online Article Text |
id | pubmed-7357563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73575632020-07-28 Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment Li, Yuan Chen, Zuhua Wu, Long Ye, Junjie Tao, Weiping PeerJ Bioinformatics BACKGROUND: Cellular heterogeneity within the tumor microenvironment is essential to tumorigenesis and tumor development. A high-resolution global view of the tumor-infiltrating immune and stromal cells in breast tumors is needed. METHODS: xCell was used to create a cellular heterogeneity map of 64 cell types in 1,092 breast tumor and adjacent normal tissues. xCell digitally dissects tissue cellular heterogeneity based on gene expression. Integrated statistical analyses were then performed. RESULTS: There were noticeable differences between the cell fractions in tumor tissues and normal tissues. Tumors displayed higher proportions of immune cells, including CD4+ Tem, CD8+ naïve T cells, and CD8+ Tcm compared with normal tissues. Immune inhibitory receptors (PD1, CTLA4, LAG3 and TIM3) were co-expressed on certain subtypes of T cells in breast tumors, and PD1 and CTLA4 were both positively correlated with CD8+ Tcm and CD8+ T cells. 28 cell types were significantly associated with overall survival in univariate analysis. CD4+ Tem, CD8+ Tcm, CD8+ T-cells, CD8+ naive T-cells, and B cells were positive prognostic factors but CD4+ naive T-cells were negative prognostic factors for breast cancer patients. TDRD6 and TTK are promising T cell and B cell targets for tumor vaccines. Endothelial cells and fibroblasts were significantly less prevalent in tumor tissues; astrocytes and mesangial cells were negatively correlated with the T stage. Mesangial cells and keratinocytes were found to be favorable prognostic factors and myocytes were negative prognostic factors. Five cell types were found to be independent prognostic factors and we used these to create a reliable prognostic model for breast cancer patients. Cellular heterogeneity was discovered among different breast cancer subtypes by Her2, ER, and PR status. Tri-negative patients had the highest fraction of immune cells while luminal type patients had the lowest. The various cells may have diverse or opposing roles in the prognosis of breast cancer patients. CONCLUSIONS: We created a uniquecellular map for the diverse heterogeneity of immune and stromal phenotypes within the breast tumor microenvironment. This map may lead to potential therapeutic targets and biomarkers with prognostic utility. PeerJ Inc. 2020-07-10 /pmc/articles/PMC7357563/ /pubmed/32728493 http://dx.doi.org/10.7717/peerj.9478 Text en ©2020 Li et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Li, Yuan Chen, Zuhua Wu, Long Ye, Junjie Tao, Weiping Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title | Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title_full | Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title_fullStr | Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title_full_unstemmed | Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title_short | Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
title_sort | cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357563/ https://www.ncbi.nlm.nih.gov/pubmed/32728493 http://dx.doi.org/10.7717/peerj.9478 |
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