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Clinical

Comparative analysis of monocytes from healthy donors, patients with metastatic breast cancer, sepsis or tuberculosis - GSE65517

Purpose

Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-Co-receptorlow/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.

Hypothesis

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Experimental Design

Peripheral blood monocytes were isolated using magnetic cell sorting from 4 patients with metastatic breast cancer, 3 healthy controls, 3 patients with sepsis and 3 patients with active tuberculosis were immediately frozen at -80°C in TRIZOL.

Experimental Variables

Breast cancer (2021 ICD-10-CM code* = C50.91)

Sepsis (2021 ICD-10-CM code* = A41)

Tuberculosis (2021 ICD-10-CM code* = A15)

Controls

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Methods

Data was handled and normalized in BASE (https://casa4.bmc.lu.se/onk/). All data was mean background corrected followed by quantile normalization. Array control probes were removed.

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65517

Microarray
Illumina HumanHT-12 v4
13 Samples Loaded: 13
Human (Homo sapiens)
Monocytes
Breast cancer, Sepsis, Tuberculosis
Total RNA was extracted with TRIZOL. Quality control was performed with Agilent 2100 Bioanalyser.
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample_title cell type disease state
GSM1599177 Primary human monocytes from patient with metastatic breast cancer #1 primary monocyte Metastatic breast cancer
GSM1599178 Primary human monocytes from patient with metastatic breast cancer #2 primary monocyte Metastatic breast cancer
GSM1599179 Primary human monocytes from patient with metastatic breast cancer #3 primary monocyte Metastatic breast cancer
GSM1599180 Primary human monocytes from patient with metastatic breast cancer #4 primary monocyte Metastatic breast cancer
GSM1599181 Primary human monocytes from healthy control #1 primary monocyte Healthy control
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Sample ID !Sample Title Cell type Disease state
GSM1599177
Primary human monocytes from patient with metastatic breast cancer #1
primary monocyte
Metastatic breast cancer
GSM1599178
Primary human monocytes from patient with metastatic breast cancer #2
primary monocyte
Metastatic breast cancer
GSM1599179
Primary human monocytes from patient with metastatic breast cancer #3
primary monocyte
Metastatic breast cancer
GSM1599180
Primary human monocytes from patient with metastatic breast cancer #4
primary monocyte
Metastatic breast cancer
GSM1599181
Primary human monocytes from healthy control #1
primary monocyte
Healthy control
GSM1599182
Primary human monocytes from healthy control #2
primary monocyte
Healthy control
GSM1599183
Primary human monocytes from healthy control #3
primary monocyte
Healthy control
GSM1599184
Primary human monocytes from patient with gram-negative sepsis #1
primary monocyte
Gram negative sepsis
GSM1599185
Primary human monocytes from patient with gram-negative sepsis #2
primary monocyte
Gram negative sepsis
GSM1599186
Primary human monocytes from patient with gram-negative sepsis #3
primary monocyte
Gram negative sepsis
GSM1599187
Primary human monocytes from patient with tuberculosis #1
primary monocyte
Tuberculosis
GSM1599188
Primary human monocytes from patient with tuberculosis #2
primary monocyte
Tuberculosis
GSM1599189
Primary human monocytes from patient with tuberculosis #3
primary monocyte
Tuberculosis

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