Tumor Microenvironment and Myeloid-Derived Suppressor Cells

Umansky, Viktor; Sevko, Alexandra

doi:10.1007/s12307-012-0126-7

Cited by 118 publications

(88 citation statements)

References 120 publications

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“…the respective tumor vasculature (18,19). In addition, they regulate activation, maintenance, and activity of antigen-specific TCs through a plethora of immune-modulatory mechanisms, involving recruitment of immune-suppressive cell populations, particularly Tregs, MDSCs, or mast cells, among others; secretion of immune-suppressive cytokines, such as TGF-β1; or expression of immune-modulatory ligands, such as PDL-1 (19)(20)(21)(22)(23)(24)(25). Regulation of TC activity in situ occurs at interindividually varying levels, and indeed, Koch et al were able to demonstrate the tumor-selective activation and cytotoxic activity in situ of small, individually varying subpopulations of CD8 + TCs in CRC (14).…”

Section: Tnf-α Expression Is Restricted To Activated Tumor-infiltratimentioning

confidence: 99%

Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

et al. 2014

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Section: Tnf-α Expression Is Restricted To Activated Tumor-infiltratimentioning

confidence: 99%

Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

et al. 2014

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“…Previous studies have demonstrated that tumor-infiltrating myeloid progenitors such as monocytes are immune-suppressive (41,42). Flow cytometry analysis revealed that tumor-infiltrating monocytic cells (Gr-1+ CD11b+) from MB49 CD14-high tumors have significantly reduced expression of MHC II, indicating possible impairment in antigen presentation to CD4 T cells (Fig.…”

Section: Cd14-mediated Signaling Is Required For Il6 Production and Lmentioning

confidence: 85%

CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer

Cheah

Chen

Sahoo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found that CD14-high cancer cells express higher levels of numerous inflammation mediators and form larger tumors compared with CD14-low cells. CD14 antigen is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein and has been shown to be critically important in the signaling pathways of Toll-like receptor (TLR). CD14 expression in this BC subpopulation of cancer cells is required for increased cytokine production and increased tumor growth. Furthermore, tumors formed by CD14-high cells are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14-high BC cells recruit and polarize monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14-low BC cells have a higher baseline cell division rate than CD14-high cells. Importantly, CD14-high cells produce factors that further increase the proliferation of CD14-low cells. Collectively, we demonstrate that CD14-high BC cells may orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.

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“…Evidence supporting a role for MDSCs in modulating MAGE-A4 expression is provided by the results of the assessment of LLC tumor cell proliferation, which demonstrated that MDSC supernatant was able to promote the growth of tumor cells and induce increased expression of MAGE-A4. MDSCs secrete multiple factors that may support the growth and survival of tumor cells (39)(40)(41)(42), and it would be of interest to confirm whether MDSCs secrete soluble factors that regulate MAGE-A4 expression. In further support of this, it has previously been reported that CT antigen expression is association with cell cycle progression and proliferation (43)(44)(45), apoptosis (13) and susceptibility of cancer cells to cytokines (46), suggesting that the CT antigen itself may be associated with prognosis.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

2015

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Abstract. The cancer-testis (CT) family of antigens are expressed in multiple types of malignant neoplasm and are silent in normal tissues, apart from the testis. Immunotherapy targeting CT antigens is a promising therapeutic strategy for treatment of solid tumors. One member of this family, melanoma-associated antigen A4 (MAGE-A4), has been demonstrated to be expressed in melanomas and lung cancer. Patients with tumors expressing the MAGE-A4 antigen exhibit specific cellular and humoral immune responses to the antigen, resulting in a favorable prognosis. Conversely, the expression of MAGE-A4 is associated with poor survival in lung cancer. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells, which are upregulated in the cancer microenvironment. Little is known regarding any potential correlation between the expression of MAGE-A4 antigens and the accumulation of MDSCs. The present study aimed to examine the association between circulating MDSC levels and MAGE-A4 expression in a mouse model of Lewis lung cancer. The expression of MAGE-A4 in tumor cells or tissues was evaluated using western blotting, while the percentage of MDSCs (CD11b + Gr-1 + ) in the blood was detected by flow cytometry. In addition, the suppressive capacity of MDSCs and the effectiveness of MDSC depletion were assessed in C57BL/6 tumor-bearing mice. MDSCs were demonstrated to upregulate MAGE-A4 expression via the phosphosphorylated-signal transducer and activator of transcription 3 705 pathway, while depletion of MDSCs decreased the tumor growth rate, prolonged median survival and enhanced the recognition of MAGE-A4 by CD8 + T cells. These findings indicated that immunotherapeutic strategies involving induction of cytotoxic T lymphocytes that target MAGE-A4, in combination with MDSC depletion, may be an effective approach to immunotherapy for cancer types with high expression of MAGE-A4.

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Tumor Microenvironment and Myeloid-Derived Suppressor Cells

Cited by 118 publications

References 120 publications

Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

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