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

Wang, Jinhu; Yang, Jianhong

doi:10.3892/br.2016.694

Cited by 28 publications

(23 citation statements)

References 25 publications

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“…Our results reinforce and expand previous studies showing significantly higher percentage of circulating Treg cells and MDSCs in patients with breast cancer, and their association with increased tumor burden ( 19 , 20 ). Treg cells from the patients evaluated in the study reported herein also displayed a suppressive/activated phenotype compared with those from healthy donors, as was indirectly indicated by the significant decrease in the percentage of Treg cells lacking both ICOS and CD39 expression.…”

Section: Discussionsupporting

confidence: 92%

Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer

et al. 2018

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Background: Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically.Methods: Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls. Transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) in 23 patients were generated using a NanoString gene profiling platform.Results: An increased percentage of immunosuppressive cells such as granulocytic MDSCs, intermediate CD14++CD16+ monocytes and CD127negCD25highFoxP3+ Treg cells was observed in patients with breast cancer, especially patients with stage 3 and 4 disease, regardless of ER status. Following neoadjuvant chemotherapy, B cell numbers decreased significantly, whereas monocyte numbers increased. Although chemotherapy had no effect on the percentage of Treg, MDSC and NK cells, the expression of inhibitory receptors CD85j, LIAR and NKG2A and activating receptors NKp30 and NKp44 on NK cells increased, concomitant with a decreased expression of NKp46 and DNAM-1 activating receptors. Transcriptomic profiling revealed a distinct group of 3 patients in the triple negative breast cancer (TNBC) cohort who expressed high levels of mRNA encoding genes predominantly involved in inflammation. The analysis of a large transcriptomic dataset derived from the tumors of patients with TNBC revealed that the expression of CD163, CXCR4, THBS1 predicted relapse-free survival.Conclusions: The peripheral blood immunome of patients with breast cancer is influenced by the presence and stage of cancer, but not by molecular subtypes. Furthermore, immune profiling coupled with transcriptomic analyses of peripheral blood cells may identify patients with TNBC that are at risk of relapse after chemotherapy.

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Section: Discussionsupporting

confidence: 92%

Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer

et al. 2018

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“…The absolute number of regulatory T cells, characterized by the expression of CD4 + CD25 + CD127 – , has been found to be higher in breast cancer patients compared to healthy controls, with numbers higher in patients with stage III or IV breast cancer than in those with stage I or II. 124 The density of regulatory T cells that infiltrate intratumor before chemotherapy has been described as the strongest predictor for survival. 125 For breast cancer, different lymphocyte sub-populations might respond differently to radiotherapy with or without chemotherapy.…”

Section: Immunological Biomarkersmentioning

confidence: 99%

Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers

Tan¹,

Yang²,

Yang³

et al. 2018

CMAR

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Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.

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“…Besides suppressing anti-tumor immunity, MDSCs also stimulate other aspects of tumor growth including tumor angiogenesis, tumor cell invasion, and formation of premetastatic niches ( Condamine et al, 2015 ). MDSCs are directly implicated in negatively impacting patient responses to cancer therapies ( Diaz-Montero et al, 2009 ; Arihara et al, 2013 ; Chen et al, 2014 ; Kawano et al, 2015 ; Romano et al, 2015 ; Lee et al, 2016 ; Tada et al, 2016 ; Wang et al, 2016 ; Wang and Yang, 2016 ), including immunotherapies ( Kimura et al, 2013 ; Martens et al, 2016 ; Sade-Feldman et al, 2016 ; Weber et al, 2016 ; Butterfield et al, 2017 ; de Coaña et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs

Mastio

Condamine

Dominguez

et al. 2019

Journal of Experimental Medicine

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We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be controlled by the down-regulation of Rb1, but not IRF8, which is known to regulate the expansion of PMN-MDSCs from classic granulocyte precursors. In cancer patients, putative MLPGs were found within the population of CXCR1+CD15−CD14+HLA-DR−/lo monocytic cells. These findings describe a mechanism of abnormal myelopoiesis in cancer and suggest potential new approaches for selective targeting of MDSCs.

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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

Cited by 28 publications

References 25 publications

Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer

Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer

Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers

Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs

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