Limits...
Enhanced 15-lipoxygenase activity and elevated eicosanoid production in kidney tumor microenvironment contribute to the inflammation and immune suppression.

Kusmartsev S - Oncoimmunology (2012)

Bottom Line: Macrophage infiltration is a hallmark in the majority of solid tumors.Our studies demonstrated that macrophages that infiltrate human renal cells carcinoma (RCC) display markedly enhanced expression and activity of 15-lipoxygenase-2 (15-LOX2).Obtained data suggest that enhanced lipoxygenase activity in tumor-associated macrophages stimulates cancer inflammation and causes immune dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Cancer and Genetics Research Center; University of Florida; Gainesville, FL USA.

ABSTRACT
Macrophage infiltration is a hallmark in the majority of solid tumors. Our studies demonstrated that macrophages that infiltrate human renal cells carcinoma (RCC) display markedly enhanced expression and activity of 15-lipoxygenase-2 (15-LOX2). Obtained data suggest that enhanced lipoxygenase activity in tumor-associated macrophages stimulates cancer inflammation and causes immune dysfunction.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Tumor-associated macrophages contribute to the cancer immune suppression and cancer inflammation in RCC via enhanced 15-LOX2/15-S-HETE pathway. Enhanced 15-LOX2 activity and elevated levels of eicosanoids of RCC tumor-microenvironment enable increased production of pro-inflammatory chemokine CCL2. Elevated levels of CCL2 in tumor lead to migration of CCR2-expressing monocytes from peripheral blood to the tumor. In tumor tissue recruited monocytes differentiate in 15-LOX-expressing tumor-associated macrophages (TAMs). High 15-LOX2 expression/activity in TAMs results in elevated secretion of arachidonate metabolites and increased production of IL-10 and CCL2 by TAMs and T cells. In addition, TAMs efficiently convert T cells into FOXP3+ T regs. Together, elevated levels of IL-10 and T regs promote local immunosuppression and T cell tolerance in RCC tumor microenvironment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3377006&req=5

Figure 1: Figure 1. Tumor-associated macrophages contribute to the cancer immune suppression and cancer inflammation in RCC via enhanced 15-LOX2/15-S-HETE pathway. Enhanced 15-LOX2 activity and elevated levels of eicosanoids of RCC tumor-microenvironment enable increased production of pro-inflammatory chemokine CCL2. Elevated levels of CCL2 in tumor lead to migration of CCR2-expressing monocytes from peripheral blood to the tumor. In tumor tissue recruited monocytes differentiate in 15-LOX-expressing tumor-associated macrophages (TAMs). High 15-LOX2 expression/activity in TAMs results in elevated secretion of arachidonate metabolites and increased production of IL-10 and CCL2 by TAMs and T cells. In addition, TAMs efficiently convert T cells into FOXP3+ T regs. Together, elevated levels of IL-10 and T regs promote local immunosuppression and T cell tolerance in RCC tumor microenvironment.

Mentions: Cancer therapy and immunomodulatory therapy of RCC is less effective in treating large tumors partly due to immune suppression associated with advanced metastatic cancer disease. Our data suggest that tumor-associated macrophages play an important role in the development of immune suppression and T cell tolerance in human RCC through secretion of immunosuppressive factors and induction of immune unresponsiveness in T cells. We demonstrated that immune suppression in RCC is closely relates to deregulated eicosanoid metabolism in the tumor microenvironment. Figure 1 provides a schematic overview of the contribution 15-LOX2-expressing tumor-associated macrophages in immune dysfunction in patients with kidney cancer. This figure illustrates that macrophages infiltrating human RCC have a significant impact on cancer inflammation via CCL2-mediated recruitment of monocytes to the tumor site10 and inhibition of generation of anti-tumor immune response via secretion of IL-10 and also by conversion of T cells into T regs.


Enhanced 15-lipoxygenase activity and elevated eicosanoid production in kidney tumor microenvironment contribute to the inflammation and immune suppression.

Kusmartsev S - Oncoimmunology (2012)

Figure 1. Tumor-associated macrophages contribute to the cancer immune suppression and cancer inflammation in RCC via enhanced 15-LOX2/15-S-HETE pathway. Enhanced 15-LOX2 activity and elevated levels of eicosanoids of RCC tumor-microenvironment enable increased production of pro-inflammatory chemokine CCL2. Elevated levels of CCL2 in tumor lead to migration of CCR2-expressing monocytes from peripheral blood to the tumor. In tumor tissue recruited monocytes differentiate in 15-LOX-expressing tumor-associated macrophages (TAMs). High 15-LOX2 expression/activity in TAMs results in elevated secretion of arachidonate metabolites and increased production of IL-10 and CCL2 by TAMs and T cells. In addition, TAMs efficiently convert T cells into FOXP3+ T regs. Together, elevated levels of IL-10 and T regs promote local immunosuppression and T cell tolerance in RCC tumor microenvironment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3377006&req=5

Figure 1: Figure 1. Tumor-associated macrophages contribute to the cancer immune suppression and cancer inflammation in RCC via enhanced 15-LOX2/15-S-HETE pathway. Enhanced 15-LOX2 activity and elevated levels of eicosanoids of RCC tumor-microenvironment enable increased production of pro-inflammatory chemokine CCL2. Elevated levels of CCL2 in tumor lead to migration of CCR2-expressing monocytes from peripheral blood to the tumor. In tumor tissue recruited monocytes differentiate in 15-LOX-expressing tumor-associated macrophages (TAMs). High 15-LOX2 expression/activity in TAMs results in elevated secretion of arachidonate metabolites and increased production of IL-10 and CCL2 by TAMs and T cells. In addition, TAMs efficiently convert T cells into FOXP3+ T regs. Together, elevated levels of IL-10 and T regs promote local immunosuppression and T cell tolerance in RCC tumor microenvironment.
Mentions: Cancer therapy and immunomodulatory therapy of RCC is less effective in treating large tumors partly due to immune suppression associated with advanced metastatic cancer disease. Our data suggest that tumor-associated macrophages play an important role in the development of immune suppression and T cell tolerance in human RCC through secretion of immunosuppressive factors and induction of immune unresponsiveness in T cells. We demonstrated that immune suppression in RCC is closely relates to deregulated eicosanoid metabolism in the tumor microenvironment. Figure 1 provides a schematic overview of the contribution 15-LOX2-expressing tumor-associated macrophages in immune dysfunction in patients with kidney cancer. This figure illustrates that macrophages infiltrating human RCC have a significant impact on cancer inflammation via CCL2-mediated recruitment of monocytes to the tumor site10 and inhibition of generation of anti-tumor immune response via secretion of IL-10 and also by conversion of T cells into T regs.

Bottom Line: Macrophage infiltration is a hallmark in the majority of solid tumors.Our studies demonstrated that macrophages that infiltrate human renal cells carcinoma (RCC) display markedly enhanced expression and activity of 15-lipoxygenase-2 (15-LOX2).Obtained data suggest that enhanced lipoxygenase activity in tumor-associated macrophages stimulates cancer inflammation and causes immune dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Cancer and Genetics Research Center; University of Florida; Gainesville, FL USA.

ABSTRACT
Macrophage infiltration is a hallmark in the majority of solid tumors. Our studies demonstrated that macrophages that infiltrate human renal cells carcinoma (RCC) display markedly enhanced expression and activity of 15-lipoxygenase-2 (15-LOX2). Obtained data suggest that enhanced lipoxygenase activity in tumor-associated macrophages stimulates cancer inflammation and causes immune dysfunction.

No MeSH data available.


Related in: MedlinePlus