Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer

Okła, Karolina; Czerwonka, Arkadiusz; Wawruszak, Anna; Bobinski, M.; Bilska, Małgorzata; Tarkowski, Rafał; Bednarek, Wiesława; Wertel, Iwona; Kotarski, Jan

doi:10.3389/fimmu.2019.00691

Cited by 70 publications

(63 citation statements)

References 53 publications

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“…Furthermore, IDO activity in peripheral blood was positively correlated with levels of circulating PD-L1 + CD8 + T-cells and CTLA-4 + Tregs, underlining the close interconnection between these immunosuppressive markers in the blood circulation (86,206). In early epithelial ovarian cancer, the level of IDO + mMDSCs and IDO + pmnMDSCs was significantly higher in the peripheral blood compared to the tumor microenvironment (207).…”

Section: Ido In the Peripheral Bloodmentioning

confidence: 87%

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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Section: Ido In the Peripheral Bloodmentioning

confidence: 87%

IDO Expression in Cancer: Different Compartment, Different Functionality?

2020

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“…Our results are in line with Cannioto et al but not with Lutgendorf et al . 21 22 Wu et al and Okla et al had already evaluated the presence of monocytic myeloid-derived suppressor cells in ovarian cancer, but only compared healthy controls with malignant cases 23 24. They concluded that cells were increased in patients with malignant tumors and that their presence correlated negatively with prognosis.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

Coosemans

Baert

Ceusters

et al. 2019

Int J Gynecol Cancer

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BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

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“…These cells play an essential role in the maintenance of self-tolerance, but may also impede anti-tumor cell-mediated immune responses and promote cancer progression [90]. Although some disagreement is evident [107], several earlier studies have reported that MDSCs induce differentiation and/or proliferation of Foxp3+ Tregs in tumor-bearing mice [89,91,92] via mechanisms which involve the production of the immunosuppressive cytokines, IL-10 and TGFß1 [93,108]. In addition, others have reported that the monocytic subset of MDSCs has the ability to recruit Tregs to the tumor site in a CCR5-dependent manner, indicating that these cells may be most prominent with respect to the attraction of Tregs to the TME [94].…”

Section: Differentiation and Expansion Of Tregsmentioning

confidence: 99%

Role of the Neutrophil in the Pathogenesis of Advanced Cancer and Impaired Responsiveness to Therapy

et al. 2020

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Notwithstanding the well-recognized involvement of chronic neutrophilic inflammation in the initiation phase of many types of epithelial cancers, a growing body of evidence has also implicated these cells in the pathogenesis of the later phases of cancer development, specifically progression and spread. In this setting, established tumors have a propensity to induce myelopoiesis and to recruit neutrophils to the tumor microenvironment (TME), where these cells undergo reprogramming and transitioning to myeloid-derived suppressor cells (MDSCs) with a pro-tumorigenic phenotype. In the TME, these MDSCs, via the production of a broad range of mediators, not only attenuate the anti-tumor activity of tumor-infiltrating lymphocytes, but also exclude these cells from the TME. Realization of the pro-tumorigenic activities of MDSCs of neutrophilic origin has resulted in the development of a range of adjunctive strategies targeting the recruitment of these cells and/or the harmful activities of their mediators of immunosuppression. Most of these are in the pre-clinical or very early clinical stages of evaluation. Notable exceptions, however, are several pharmacologic, allosteric inhibitors of neutrophil/MDSC CXCR1/2 receptors. These agents have entered late-stage clinical assessment as adjuncts to either chemotherapy or inhibitory immune checkpoint-targeted therapy in patients with various types of advanced malignancy. The current review updates the origins and identities of MDSCs of neutrophilic origin and their spectrum of immunosuppressive mediators, as well as current and pipeline MDSC-targeted strategies as potential adjuncts to cancer therapies. These sections are preceded by a consideration of the carcinogenic potential of neutrophils.

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Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer

Cited by 70 publications

References 53 publications

IDO Expression in Cancer: Different Compartment, Different Functionality?

IDO Expression in Cancer: Different Compartment, Different Functionality?

Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

Role of the Neutrophil in the Pathogenesis of Advanced Cancer and Impaired Responsiveness to Therapy

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