Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer

Li, Fangxuan; Yang, Zhao; Wei, Lijuan; Li, Shixia; Liu, Juntian

doi:10.1080/15384047.2018.1450116

Cited by 117 publications

(88 citation statements)

References 40 publications

(58 reference statements)

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“…IDO activity is an important mechanism by which effector T cells can be induced and converted to Tregs. The IDO-mediated depletion of tryptophan and subsequent production of immunosuppressive products may also lead to T cell suppression through the down-regulation of the TCR-CD3-z chain [34]. IDO high MDSCs suppress both T-cell activation and proliferation in untreated CLL patients [16].…”

Section: Discussionmentioning

confidence: 99%

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Kowalska

2020

Folia Histochem Cytobiol.

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Introduction. Myeloid derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment. The accumulation of MDSCs has been demonstrated in many types of human solid tumors. However, the relevance of this heterogeneous population in hematopoietic malignancies has only recently gained stronger attention. MDSCs are a phenotypically and functionally heterogeneous group of cells. The results of recent studies indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) affects a monocytic MDSC (M-MDSC) subpopulation. This study aimed to analyze the frequency of M-MDSCs with intracellular IL-10 and TGF-b1 expression in newly diagnosed CLL patients. We investigated the potential role of M-MDSCs in CLL by analyzing the level of IL-10 and TGF-b1 expression in circulating M-MDSCs in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. Material and methods. Seventy CLL patients and 17 age-matched healthy volunteers were included in this study. Flow cytometric detection of Mo-MDSCs (CD14 + CD11b + CD15-HLA-DR-/low) with intracellular IL-10 and TGF-b1 expression was done. Results. We found a significantly higher median percentage of M-MDSC with IL-10 or TGF-b1 expression in CLL patients than in healthy volunteers. The percentage of M-MDSC with intracellular IL-10 or TGF-b1 expression was significantly lower in CLL patients at stage 0 as compared to the stages I/II and III/IV according to Rai stages. The percentage of M-MDSC with intracellular TGF-b1 expression was significantly higher in ZAP-70-positive and CD38-positive patients compared with ZAP-70-negative and group of CD38-negative ones. There was also a significantly higher percentage of M-MDSC positive for intracellular TGF-b expression in patients carrying the 11q22.3 and/or the 17p13.1 deletion than in patients without these genetic aberrations. The percentage of M-MDSC IL-10-positive and M-MDSC TGF-b1-positive measured at the time of diagnosis was higher in patients requiring therapy as compared to patients without treatment during the observation period. Conclusion. In conclusion, we have shown that an increased percentage of M-MDSC cells producing IL-10 and TGF-b1 in CLL patients may be associated with the suppression of the immune response against CLL. It can be assumed that the increased percentage of M-MDSC with an intracellular expression of IL-10 and TGF-b1 may be used in the future as the factor defining the group of patients with shorter time to onset of treatment.

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Section: Discussionmentioning

confidence: 99%

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Kowalska

2020

Folia Histochem Cytobiol.

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“…MDSCs are also capable of expressing IDO, promoting tumor growth, and T-cell inhibition. The frequency of IDO + MDSCs was positively associated with the amount of FoxP3 + Tregs and had a negative impact on patient outcome in breast cancer patients receiving neoadjuvant chemotherapy (75). In the tumor microenvironment of murine lung cancer models a subgroup of monocytic (Gr1 int CD11b + ) MDSCs were defined as the main source of IDO expression (79).…”

Section: Immune Cellsmentioning

confidence: 99%

IDO Expression in Cancer: Different Compartment, Different Functionality?

2020

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Indoleamine 2,3-dioxygenase 1 (IDO1) is a cytosolic haem-containing enzyme involved in the degradation of tryptophan to kynurenine. Although initially thought to be solely implicated in the modulation of innate immune responses during infection, subsequent discoveries demonstrated IDO1 as a mechanism of acquired immune tolerance. In cancer, IDO1 expression/activity has been observed in tumor cells as well as in the tumor-surrounding stroma, which is composed of endothelial cells, immune cells, fibroblasts, and mesenchymal cells. IDO1 expression/activity has also been reported in the peripheral blood. This manuscript reviews available data on IDO1 expression, mechanisms of its induction, and its function in cancer for each of these compartments. In-depth study of the biological function of IDO1 according to the expressing (tumor) cell can help to understand if and when IDO1 inhibition can play a role in cancer therapy.

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“…Among them, Treg cells, MDSCs and macrophages are mainly involved in the immunosuppressive action (Vasaturo et al 2015) via the secretion of key molecules, such as transforming growth factor beta (TGF-β), prostaglandin E2, indoleamine 2,3-dioxygenase and interleukin (IL)-10 (Capietto et al 2011). The abundance of Tregs, MDSCs and TAMs in the stroma also helps cancer cells to escape immune surveillance and is associated with worse prognosis (Mantovani et al 2006, Greten et al 2011, Bergenfelz et al 2015, Li et al 2018, whereas CTLs are associated with a good prognosis (Tosolini et al 2011). Signals derived from cancer cells and the stroma determine the TAM phenotype from M1, which stimulates immunoprotective inflammatory responses, and M2, which has an immunosuppressive action.…”

Section: Mechanisms Of Immune Suppression or Immune Escapementioning

confidence: 99%

Tumour growth and immune evasion as targets for a new strategy in advanced cancer

Nicolini¹,

Rossi²,

Carpi³

2018

Endocrine-Related Cancer

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It has become clearer that advanced cancer, especially advanced breast cancer, is an entirely displayed pathological system that is much more complex than previously considered. However, the direct relationship between tumour growth and immune evasion can represent a general rule governing the pathological cancer system from the initial cancer cells to when the system is entirely displayed. Accordingly, a refined pathobiological model and a novel therapeutic strategy are proposed. The novel therapeutic strategy is based on therapeutically induced conditions (undetectable tumour burden and/or a prolonged tumour 'resting state'), which enable an efficacious immune response in advanced breast and other types of solid cancers.

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Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer

Cited by 117 publications

References 40 publications

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

IDO Expression in Cancer: Different Compartment, Different Functionality?

Tumour growth and immune evasion as targets for a new strategy in advanced cancer

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