Identification of CD4+CD25+CD127− regulatory T cells and CD14+HLA−DR−/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer

Abstract Identification of the different elements intervening at the immunoedition process, in each body compartment, seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40+ and PD-1+ T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer, were analyzed prior to and along the implementation of first line antineoplastic therapy. Subsequently, a formal comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients basally showed higher levels of myeloid derived suppressor cells (35.43, IR=180.73 vs 17.53, IR=16.96 cells/μl; p=0.001) and regulatory T cells (32.05, IR=29.84 vs 22.61, IR=13.57 cells/μl; p=0.001) in comparison with healthy women. Furthermore, after therapy, an increase in the number of activated T lymphocytes (expressing OX40), and a decrease of immune inhibitory cells (MDSCs, and Tregs), and the number of inhibited (or exhausted) T lymphocytes (expressing PD-1), could be ascertained in patients with clinical benefit (p≤0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be clearly correlated with clinical evolution, at least in ABC.

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Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

Scientific Reports ◽

10.1038/s41598-021-93838-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Natalia Palazón-Carrión ◽

Carlos Jiménez-Cortegana ◽

M. Luisa Sánchez-León ◽

Fernando Henao-Carrasco ◽

Esteban Nogales-Fernández ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Advanced Breast Cancer ◽

Peripheral Blood ◽

Clinical Benefit ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Immune Biomarkers

AbstractIdentification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40 + and PD-1 + T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer were analyzed along of first line antineoplastic therapy. Subsequently, a comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients showed higher basal levels of myeloid derived suppressor cells (35.43, IR = 180.73 vs 17.53, IR = 16.96 cells/μl; p = 0.001) and regulatory T cells (32.05, IR = 29.84 vs 22.61, IR = 13.57 cells/μl; p = 0.001) in comparison with healthy women. Furthermore, an increase in the number of activated T lymphocytes (expressing OX40), a decrease of immune inhibitory cells (MDSCs and Tregs) and inhibited T lymphocytes (expressing PD-1) were observed along the treatment in patients with clinical benefit (p ≤ 0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be correlated with clinical evolution, at least in ABC.

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Increased Level of both CD4+FOXP3+ Regulatory T Cells and CD14+HLA-DR−/low Myeloid-Derived Suppressor Cells and Decreased Level of Dendritic Cells in Patients with Multiple Myeloma

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.2010.02463.x ◽

2010 ◽

Vol 72 (6) ◽

pp. 540-547 ◽

Cited By ~ 132

Author(s):

M. K. Brimnes ◽

A. J. Vangsted ◽

L. M. Knudsen ◽

P. Gimsing ◽

A. O. Gang ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Hla Dr

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STAT3 Silencing and TLR7/8 Pathway Activation Repolarize and Suppress Myeloid-Derived Suppressor Cells From Breast Cancer Patients

Frontiers in Immunology ◽

10.3389/fimmu.2020.613215 ◽

2021 ◽

Vol 11 ◽

Author(s):

Elham Safarzadeh ◽

Ali Mohammadi ◽

Behzad Mansoori ◽

Pascal H. G. Duijf ◽

Shahryar Hashemzadeh ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Cell ◽

Cancer Cells ◽

Cancer Patients ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Breast Cancer Patients ◽

Hla Dr ◽

Stat3 Inhibition

Cancer cells escape immune destruction. From this perspective, myeloid-derived suppressor cells (MDSCs), which are immunosuppressive in various cancers including breast cancer (BC), are significant. However, the precise mechanisms are unknown. We isolated HLA-DR-CD33+ MDSCs and CD3+ T cells from BC patients’ peripheral blood and healthy donors through MACS and immunophenotyped by flow cytometry. Transfection of short-interfering RNAs and treatment with a TLR7/8 agonist altered pathway activities in vitro. Gene expression was analyzed using qRT-PCR, western blotting, and immunohistochemistry. Our findings showed an association between the progression of BC and increased levels of circulating HLA-DR-CD33+ MDSCs. These cells strongly suppress both autologous and analogous CD3+ T cell proliferation and enter the tumor microenvironment. We also identified increased STAT3 signaling and increased IDO and IL-10 expression in BC-derived MDSCs as immunosuppression mechanisms. Further, STAT3 inhibition and TLR7/8 pathway stimulation reduce the immunosuppressive activity of patient-derived MDSCs on T cells by inducing MDSC repolarization and differentiation into mature myeloid cells. This also alters the expression of critical cytokines and transcription factors in CD3+ T cells and, importantly, reduces breast cancer cells’ proliferation. Finally, while chemotherapy is able to significantly reduce circulating MDSCs’ level in patients with breast cancer, these MDSCs remained highly T cell-suppressive. We identified a novel molecular mechanism of MDSC-mediated immunosuppression. STAT3 inhibition and TLR7/8 pathway stimulation in MDSCs repolarize and suppress MDSCs from breast cancer patients. This offers new opportunities for BC immunotherapy.

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