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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 regulatory T cells (Treg) in the tumor microenvironment: a schematic overview of the most important immunosuppressive mechanisms through which regulatory T cells function and the possibility of feedback-loops. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyses the oxidative catabolism of tryptophan. IDO suppresses T cell responses and promotes immune tolerance in mammalian pregnancy, tumor resistance, chronic infection, autoimmunity and allergic inflammation. TGF-β: transforming growth factor-β; APC: antigen presenting cell; MHC: major histocompatibility complex; CD: cluster of differentiation.
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Figure 1: The role of regulatory T cells (Treg) in the tumor microenvironment: a schematic overview of the most important immunosuppressive mechanisms through which regulatory T cells function and the possibility of feedback-loops. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyses the oxidative catabolism of tryptophan. IDO suppresses T cell responses and promotes immune tolerance in mammalian pregnancy, tumor resistance, chronic infection, autoimmunity and allergic inflammation. TGF-β: transforming growth factor-β; APC: antigen presenting cell; MHC: major histocompatibility complex; CD: cluster of differentiation.

Mentions: Regulatory T cells (Treg) are a subpopulation of T cells, which maintain tolerance to self-antigens by influencing the activity of other Teff. Their physiological function is to prevent auto-immunity and down regulate undesired T cell responses. We can differentiate between 2 subsets of regulatory T cells. The naturally occurring Treg develop in the thymus and are responsible for central inhibition of auto-immunity. T cells that leave the bone marrow migrate to the thymus to mature. In the thymus auto-reactive T cells are deleted. Adaptive Treg develop as a consequence of continued peripheral T cell activation, as is present in chronic inflammation and tumor development. Treg are trafficked to the tumor site through presence of chemokines such as CCL2 and CCL22 in the tumor microenvironment. Expansion of Tregs can be induced by tolerogenic dendritic cells (DCs) through the expression of indoleamine 2,3-dioxygenase (IDO). Transforming epidermal growth factor beta (TGF-β) can convert effector T cells into regulatory T cells leading to further increase immunosuppression (Gajewski et al., 2013). Treg exert their immunosuppressive function through several mechanisms as depicted in Figure 1 (Zou, 2006). Treg will promote IDO expression and lead to depletion of tryptophan. This leads to T cell anergy and apoptosis of T cells. Furthermore stimulation of IDO will also stimulate a feedback loop by inducing tolerogenic DCs (Katz et al., 2008). Treg will also increase their expression of negative co-stimulatory molecules, such as Programmed Death-1 (PD-1), Programmed Death Ligand 1(PD-L1) and CTLA-4, leading to increased apoptosis in Teff (Ooi et al., 2014). Treg will also secrete IL-10 and TGF-β. IL-10 is an anti-inflammatory cytokine that will cause dysfunction of antigen presenting cells (APC) through decreased expression of MHC molecules and other co-stimulatory molecules and a decrease in circulating IL-12 (Maloy et al., 2001; Zheng et al., 2004). Secretion of TGF-β causes unresponsiveness in tumor infiltrating effector T cells through FoxP1 transcription factor expression (Zheng et al., 2004; Stephen et al., 2014). Parallel to IDO, TGF-β expression will stimulate an immunosuppressive feedback-loop to stimulate the transformation of Teff to Treg (Zou, 2006).


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 regulatory T cells (Treg) in the tumor microenvironment: a schematic overview of the most important immunosuppressive mechanisms through which regulatory T cells function and the possibility of feedback-loops. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyses the oxidative catabolism of tryptophan. IDO suppresses T cell responses and promotes immune tolerance in mammalian pregnancy, tumor resistance, chronic infection, autoimmunity and allergic inflammation. TGF-β: transforming growth factor-β; APC: antigen presenting cell; MHC: major histocompatibility complex; CD: cluster of differentiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The role of regulatory T cells (Treg) in the tumor microenvironment: a schematic overview of the most important immunosuppressive mechanisms through which regulatory T cells function and the possibility of feedback-loops. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyses the oxidative catabolism of tryptophan. IDO suppresses T cell responses and promotes immune tolerance in mammalian pregnancy, tumor resistance, chronic infection, autoimmunity and allergic inflammation. TGF-β: transforming growth factor-β; APC: antigen presenting cell; MHC: major histocompatibility complex; CD: cluster of differentiation.
Mentions: Regulatory T cells (Treg) are a subpopulation of T cells, which maintain tolerance to self-antigens by influencing the activity of other Teff. Their physiological function is to prevent auto-immunity and down regulate undesired T cell responses. We can differentiate between 2 subsets of regulatory T cells. The naturally occurring Treg develop in the thymus and are responsible for central inhibition of auto-immunity. T cells that leave the bone marrow migrate to the thymus to mature. In the thymus auto-reactive T cells are deleted. Adaptive Treg develop as a consequence of continued peripheral T cell activation, as is present in chronic inflammation and tumor development. Treg are trafficked to the tumor site through presence of chemokines such as CCL2 and CCL22 in the tumor microenvironment. Expansion of Tregs can be induced by tolerogenic dendritic cells (DCs) through the expression of indoleamine 2,3-dioxygenase (IDO). Transforming epidermal growth factor beta (TGF-β) can convert effector T cells into regulatory T cells leading to further increase immunosuppression (Gajewski et al., 2013). Treg exert their immunosuppressive function through several mechanisms as depicted in Figure 1 (Zou, 2006). Treg will promote IDO expression and lead to depletion of tryptophan. This leads to T cell anergy and apoptosis of T cells. Furthermore stimulation of IDO will also stimulate a feedback loop by inducing tolerogenic DCs (Katz et al., 2008). Treg will also increase their expression of negative co-stimulatory molecules, such as Programmed Death-1 (PD-1), Programmed Death Ligand 1(PD-L1) and CTLA-4, leading to increased apoptosis in Teff (Ooi et al., 2014). Treg will also secrete IL-10 and TGF-β. IL-10 is an anti-inflammatory cytokine that will cause dysfunction of antigen presenting cells (APC) through decreased expression of MHC molecules and other co-stimulatory molecules and a decrease in circulating IL-12 (Maloy et al., 2001; Zheng et al., 2004). Secretion of TGF-β causes unresponsiveness in tumor infiltrating effector T cells through FoxP1 transcription factor expression (Zheng et al., 2004; Stephen et al., 2014). Parallel to IDO, TGF-β expression will stimulate an immunosuppressive feedback-loop to stimulate the transformation of Teff to Treg (Zou, 2006).

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