Myeloid-Derived Suppressor Cell Function in Breast Cancer Patients

The incidence of breast cancer increases annually, and it has become common within families of breast cancer patients. Interleukin-2 activates cytotoxic T lymphocytes, which are important for cancer immunity. To identify markers of increased familial breast cancer risk, soluble interleukin-2 receptor levels and immunologic factors were investigated in familial breast cancer and non-familial breast cancer patients. Of 106 untreated breast cancer patients in this study, 24 had familial breast cancer and 82 had non-familial breast cancer. The patients’ soluble interleukin-2 receptor, interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, and their neutrophil-to-lymphocyte ratios were measured, and their prognoses were compared according to the soluble interleukin-2 receptor levels. Additionally, postoperative tissues from the patients with high soluble interleukin-2 receptor levels were stained with programmed cell death ligand 1 and cluster of differentiation 8. The soluble interleukin-2 receptor level in the familial breast cancer patients was significantly higher, and it showed significantly stronger correlations with the neutrophil-to-lymphocyte ratio and the interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, than in the non-familial breast cancer patients. The regulatory T cell and myeloid-derived suppressor cell levels were significantly higher in the patients with high soluble interleukin-2 receptor levels, and the overall survival and disease-free-survival rates were significantly worse for the familial breast cancer patients than for the non-familial breast cancer patients. Triple-negative breast cancer tissues from the familial breast cancer patients with high soluble interleukin-2 receptor levels stained well for programmed cell death ligand 1 and cluster of differentiation 8. Soluble interleukin-2 receptor levels can be used to predict the prognosis of familial breast cancer patients. Prospectively identifying patients who are less likely to have non-familial breast cancer is vital for improving their overall survival.

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Association of lytic effector cell function with high expression of HER-2 expression in breast cancer patients

European Journal of Cancer ◽

10.1016/0959-8049(93)90949-g ◽

1993 ◽

Vol 29 ◽

pp. S64

Author(s):

C. Wiltschke ◽

M. Krainer ◽

A. Budinski ◽

E. Tyl ◽

P. Speiser ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Effector Cell ◽

Cell Function ◽

High Expression ◽

Breast Cancer Patients ◽

Her 2

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High PKCλ expression is required for ALDH1-positive cancer stem cell function and indicates a poor clinical outcome in late-stage breast cancer patients

PLoS ONE ◽

10.1371/journal.pone.0235747 ◽

2020 ◽

Vol 15 (7) ◽

pp. e0235747

Author(s):

Yuka Nozaki ◽

Hitomi Motomura ◽

Shoma Tamori ◽

Yumiko Kimura ◽

Chotaro Onaga ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Clinical Outcome ◽

Cancer Stem Cell ◽

Cancer Patients ◽

Late Stage ◽

Cell Function ◽

Breast Cancer Patients ◽

Poor Clinical Outcome

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Germline variants associated with leukocyte genes predict tumor recurrence in breast cancer patients

npj Precision Oncology ◽

10.1038/s41698-019-0100-7 ◽

2019 ◽

Vol 3 (1) ◽

Cited By ~ 9

Author(s):

Jean-Sébastien Milanese ◽

Chabane Tibiche ◽

Jinfeng Zou ◽

Zhigang Meng ◽

Andre Nantel ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Outcomes ◽

Cell Function ◽

Recurrence Score ◽

Oncotype Dx ◽

Breast Cancer Patients ◽

Sequencing Data ◽

Germline Variants ◽

Gene Signatures

Abstract Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5–10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n = 755) cancer patients. Gene signatures derived from the genes containing functionally germline variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n = 200 and 295, P = 1.4 × 10−3). Furthermore, we compared our results with the widely known Oncotype DX test (i.e., Oncotype DX breast cancer recurrence score) and outperformed prediction for both high- and low-risk groups. Finally, we found that recurred patients possessed a higher rate of germline variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation, and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes in breast cancer.

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Modulation of suppressor cell activities by cyclophosphamide in breast cancer patients

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.1860080302 ◽

1994 ◽

Vol 8 (3) ◽

pp. 123-127 ◽

Cited By ~ 6

Author(s):

Katsumasa Kuroi ◽

Yukio Sato ◽

Yoshiyuki Yamaguchi ◽

Tetsuya Toge

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Suppressor Cell ◽

Breast Cancer Patients

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Germline genetic variants associated with leukocyte-genes predict tumor recurrence in breast cancer patients

10.1101/312355 ◽

2018 ◽

Author(s):

Jean-Sébastien Milanese ◽

Chabane Tibiche ◽

Jinfeng Zou ◽

Zhi Gang Meng ◽

Andre Nantel ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Outcomes ◽

Genetic Variants ◽

Cell Function ◽

Breast Cancer Patients ◽

Sequencing Data ◽

Germline Variants ◽

Gene Signatures ◽

Cytokine Interactions

AbstractGermline genetic variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5-10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n=755) cancer patients. Gene signatures derived from the genes containing functionally germline genetic variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n=200 and 295, P=1.4×10−3). Furthermore, we found that recurred patients possessed a higher rate of germline genetic variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes (or drug response) in breast cancer, other cancer types and even other complex diseases.

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