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Immunological parameters as a new lead in the diagnosis of ovarian cancer.

Baert T, Timmerman D, Vergote I, Coosemans A - Facts Views Vis Obgyn (2015)

Bottom Line: Prognosis is poor in women diagnosed at stage III to IV or in case disease recurs.The study of the immune system as a valuable parameter in the development of ovarian cancer has been neglected for a long time.Nevertheless, this is a field in full progression and might open new perspectives in the diagnosis and prognosis of ovarian cancer patients and could lead to a more motivated choice of targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: UZ Leuven, Gynaecology and Obstetrics, Herestraat 49, 3000 Leuven, Belgium. ; Department of Oncology, Leuven Cancer Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

ABSTRACT
Ovarian cancer is the leading cause of pelvic gynecological cancer death in Europe. Prognosis is poor in women diagnosed at stage III to IV or in case disease recurs. Platin-based chemotherapy and radical surgery have already improved prognosis significantly. Novel strategies in the treatment of ovarian cancer are being searched for. The study of the immune system as a valuable parameter in the development of ovarian cancer has been neglected for a long time. Nevertheless, this is a field in full progression and might open new perspectives in the diagnosis and prognosis of ovarian cancer patients and could lead to a more motivated choice of targeted therapies.

No MeSH data available.


Related in: MedlinePlus

The role of Myeloid Derived Supressor Cells (MDSC) in the tumor microenvironment: an overview of the most relevant immunomodulatory functions of tumor associated myeloid derived suppressor cells stimulating immunosuppressive cells and inhibiting anti-tumor effector cells. Treg: regulatory T cell; DC: dendritic cell; NK cell: natural killer cell.
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Figure 2: The role of Myeloid Derived Supressor Cells (MDSC) in the tumor microenvironment: an overview of the most relevant immunomodulatory functions of tumor associated myeloid derived suppressor cells stimulating immunosuppressive cells and inhibiting anti-tumor effector cells. Treg: regulatory T cell; DC: dendritic cell; NK cell: natural killer cell.

Mentions: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors at different stages of differentiation. These cells are capable of suppressing the innate (natural killer cells (NK)/non-specific defense) and the adaptive immune system (Teff/specific defense mechanisms). MDSC are influenced by pro-inflammatory cytokines and their presence in the tumor microenvironment could be one of the causes of tumor-associated immunosuppression. The presence of circulating MDSC correlates with poor prognosis, increased metastatic potential and tumor evasion of host immunity. As depicted in Figure 2, the accumulation of MDSC in the tumor microenvironment is stimulated by several factors such as: granulocyte macrophage colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), chemokines such as CCL-2 and TGF-β, produced by the tumor and the intratumoral immune cells (Nagaraj et al., 2010; Talmadge et al., 2013). MDSC will recruit and induce Treg through production of IL-10 and TGF-β and the expression of chemotactic molecules on the cell surface of the MDSC. MDSC are myeloid lineage cells and can differentiate into DC when matured; however influenced by the tumor environment they will lead to tolerogenic IDO-producing DCs (Gabrilovich et al., 2012). MDSC will inhibit NK cells and cause T cell anergy through the production of TGF-β. As TGF-β is also one of the molecules that will attract MDSC this will again cause a positive feedback loop. MDSC will also inhibit the function of NK cells through interaction with their NK cell receptor NKp30. Therefore MDSC are the main negative regulator of NK cell function in a tumor-bearing host (Hoechst et al., 2009; Li et al., 2009). The main immunosuppressive role of MDSCs is the inhibition of T cell activation and proliferation. In general tumor-associated MDSC will deprive T cells of amino-acids, such as L-arginine necessary for their proliferation. MDSC will inhibit activation of the T cell through oxidation or nitrosylation of the T-cell receptor. Furthermore MDSCs will interfere with T cell migration and viability (Gabrilovich et al., 2012).


Immunological parameters as a new lead in the diagnosis of ovarian cancer.

Baert T, Timmerman D, Vergote I, Coosemans A - Facts Views Vis Obgyn (2015)

The role of Myeloid Derived Supressor Cells (MDSC) in the tumor microenvironment: an overview of the most relevant immunomodulatory functions of tumor associated myeloid derived suppressor cells stimulating immunosuppressive cells and inhibiting anti-tumor effector cells. Treg: regulatory T cell; DC: dendritic cell; NK cell: natural killer cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402445&req=5

Figure 2: The role of Myeloid Derived Supressor Cells (MDSC) in the tumor microenvironment: an overview of the most relevant immunomodulatory functions of tumor associated myeloid derived suppressor cells stimulating immunosuppressive cells and inhibiting anti-tumor effector cells. Treg: regulatory T cell; DC: dendritic cell; NK cell: natural killer cell.
Mentions: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors at different stages of differentiation. These cells are capable of suppressing the innate (natural killer cells (NK)/non-specific defense) and the adaptive immune system (Teff/specific defense mechanisms). MDSC are influenced by pro-inflammatory cytokines and their presence in the tumor microenvironment could be one of the causes of tumor-associated immunosuppression. The presence of circulating MDSC correlates with poor prognosis, increased metastatic potential and tumor evasion of host immunity. As depicted in Figure 2, the accumulation of MDSC in the tumor microenvironment is stimulated by several factors such as: granulocyte macrophage colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), chemokines such as CCL-2 and TGF-β, produced by the tumor and the intratumoral immune cells (Nagaraj et al., 2010; Talmadge et al., 2013). MDSC will recruit and induce Treg through production of IL-10 and TGF-β and the expression of chemotactic molecules on the cell surface of the MDSC. MDSC are myeloid lineage cells and can differentiate into DC when matured; however influenced by the tumor environment they will lead to tolerogenic IDO-producing DCs (Gabrilovich et al., 2012). MDSC will inhibit NK cells and cause T cell anergy through the production of TGF-β. As TGF-β is also one of the molecules that will attract MDSC this will again cause a positive feedback loop. MDSC will also inhibit the function of NK cells through interaction with their NK cell receptor NKp30. Therefore MDSC are the main negative regulator of NK cell function in a tumor-bearing host (Hoechst et al., 2009; Li et al., 2009). The main immunosuppressive role of MDSCs is the inhibition of T cell activation and proliferation. In general tumor-associated MDSC will deprive T cells of amino-acids, such as L-arginine necessary for their proliferation. MDSC will inhibit activation of the T cell through oxidation or nitrosylation of the T-cell receptor. Furthermore MDSCs will interfere with T cell migration and viability (Gabrilovich et al., 2012).

Bottom Line: Prognosis is poor in women diagnosed at stage III to IV or in case disease recurs.The study of the immune system as a valuable parameter in the development of ovarian cancer has been neglected for a long time.Nevertheless, this is a field in full progression and might open new perspectives in the diagnosis and prognosis of ovarian cancer patients and could lead to a more motivated choice of targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: UZ Leuven, Gynaecology and Obstetrics, Herestraat 49, 3000 Leuven, Belgium. ; Department of Oncology, Leuven Cancer Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

ABSTRACT
Ovarian cancer is the leading cause of pelvic gynecological cancer death in Europe. Prognosis is poor in women diagnosed at stage III to IV or in case disease recurs. Platin-based chemotherapy and radical surgery have already improved prognosis significantly. Novel strategies in the treatment of ovarian cancer are being searched for. The study of the immune system as a valuable parameter in the development of ovarian cancer has been neglected for a long time. Nevertheless, this is a field in full progression and might open new perspectives in the diagnosis and prognosis of ovarian cancer patients and could lead to a more motivated choice of targeted therapies.

No MeSH data available.


Related in: MedlinePlus