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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment
Yuan Li1, Zuhua Chen2, Long Wu1
1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
Insights
This study maps cellular heterogeneity in breast tumors, revealing distinct immune and stromal cell profiles. Certain cell types correlate with patient survival, offering potential therapeutic targets and prognostic biomarkers.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Tumor microenvironment cellular heterogeneity is crucial for cancer development.
- A detailed understanding of immune and stromal cells in breast tumors is needed.
Purpose of the Study:
- To create a high-resolution cellular heterogeneity map of breast tumors.
- To identify cell types associated with prognosis and potential therapeutic targets.
Main Methods:
- Utilized xCell to analyze gene expression data from 1,092 breast tumor and normal tissues.
- Created a cellular heterogeneity map encompassing 64 cell types.
- Performed integrated statistical analyses to correlate cell types with clinical outcomes.
Main Results:
- Breast tumors exhibit significantly different cell fractions compared to normal tissues, with higher immune cell proportions.
- Specific T cell subtypes (CD4+ Tem, CD8+ Tcm, CD8+ naïve T cells) and B cells are associated with improved survival.
- Identified TDRD6 and TTK as potential targets for tumor vaccines; discovered prognostic roles for endothelial cells, fibroblasts, astrocytes, mesangial cells, keratinocytes, and myocytes.
- Developed a prognostic model based on five independent cell types and observed heterogeneity across breast cancer subtypes (Her2, ER, PR status).
Conclusions:
- A comprehensive cellular map of breast tumor microenvironment phenotypes was generated.
- This map provides potential therapeutic targets and prognostic biomarkers for breast cancer.
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.
