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Chronic liver inflammation dominated by interferon-γ can prevent hepatocarcinogenesis.

Schrader J, Herkel J - Oncoimmunology (2012)

Bottom Line: Inflammation is a major stimulus for carcinogenesis; however inflammation can also inhibit tumor growth and deplete malignant cells.The differences between cancer-promoting and cancer-inhibitory inflammation are not clear.We identified Interferon-γ as a major mediator of cancer-inhibitory inflammation that promotes anti-cancer immunity in the liver and sensitizes malignant hepatocytes for apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine I; University Medical Centre Hamburg-Eppendorf; Hamburg, Germany.

ABSTRACT
Inflammation is a major stimulus for carcinogenesis; however inflammation can also inhibit tumor growth and deplete malignant cells. The differences between cancer-promoting and cancer-inhibitory inflammation are not clear. We identified Interferon-γ as a major mediator of cancer-inhibitory inflammation that promotes anti-cancer immunity in the liver and sensitizes malignant hepatocytes for apoptosis.

No MeSH data available.


Related in: MedlinePlus

Figure 1. A model of cancer-promoting and cancer-inhibitory liver inflammation. Tumor-suppressive inflammatory liver infiltrates are characterized by high content of IFNγ-secreting lymphocytes (Th1, CD8 T, NK and NKT cells), sustained activation of the STAT1 pathway in hepatocytes, macrophage polarization toward an M1 phenotype and fibrolysis. In contrast, tumor-promoting liver infiltrates are characterized by high content of IFNγ non-producing or interleukin-22 producing lymphocytes, interleukin-6 secretion by various cell types, macrophages with M2 phenotype, sustained STAT3 activation in hepatocytes, fibrogenesis and angiogenesis.
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Figure 1: Figure 1. A model of cancer-promoting and cancer-inhibitory liver inflammation. Tumor-suppressive inflammatory liver infiltrates are characterized by high content of IFNγ-secreting lymphocytes (Th1, CD8 T, NK and NKT cells), sustained activation of the STAT1 pathway in hepatocytes, macrophage polarization toward an M1 phenotype and fibrolysis. In contrast, tumor-promoting liver infiltrates are characterized by high content of IFNγ non-producing or interleukin-22 producing lymphocytes, interleukin-6 secretion by various cell types, macrophages with M2 phenotype, sustained STAT3 activation in hepatocytes, fibrogenesis and angiogenesis.

Mentions: We thus propose that the differences between tumor-promoting and tumor-inhibitory liver inflammation may be explained not only by the degree of cytotoxic activity of inflammatory cells, but also by predominance of either STAT1-activating cytokines, such as IFNγ, or STAT3-activating cytokines, such as interleukin-6 or interleukin-22 (Fig. 1). This model is compatible with the finding that the balance of STAT1 and STAT3 activation seems to predict the clinical outcome in cutaneous melanoma.9 During tumor promotion, the presence or absence of IFNγ further influences the tumor microenvironment and tissue remodelling. Indeed, IFNγ is known to promote macrophage polarization toward an M1 phenotype and to inhibit fibrogenesis, whereas M2 macrophages, which are induced by non-IFNγ producing lymphocytes and malignant hepatocytes, promote fibrogenesis and angiogenesis. It is conceivable that the presence of IFNγ during tumor promotion may prevent induction of M2 macrophages. In summary, inflammatory infiltrates with high content of IFNγ-secreting lymphocytes, i.e., Th1 cells, CD8 T cells, some NK cells and some NKT cells, may characterize tumor-suppressive inflammation, whereas infiltrates with high content of IFNγ non-producing or interleukin-22 producing lymphocytes may characterize tumor-promoting infiltrates. Therefore, manipulating the type of chronic inflammation and the composition of tumor-associated inflammatory infiltrates may serve the prevention of cancer.


Chronic liver inflammation dominated by interferon-γ can prevent hepatocarcinogenesis.

Schrader J, Herkel J - Oncoimmunology (2012)

Figure 1. A model of cancer-promoting and cancer-inhibitory liver inflammation. Tumor-suppressive inflammatory liver infiltrates are characterized by high content of IFNγ-secreting lymphocytes (Th1, CD8 T, NK and NKT cells), sustained activation of the STAT1 pathway in hepatocytes, macrophage polarization toward an M1 phenotype and fibrolysis. In contrast, tumor-promoting liver infiltrates are characterized by high content of IFNγ non-producing or interleukin-22 producing lymphocytes, interleukin-6 secretion by various cell types, macrophages with M2 phenotype, sustained STAT3 activation in hepatocytes, fibrogenesis and angiogenesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376979&req=5

Figure 1: Figure 1. A model of cancer-promoting and cancer-inhibitory liver inflammation. Tumor-suppressive inflammatory liver infiltrates are characterized by high content of IFNγ-secreting lymphocytes (Th1, CD8 T, NK and NKT cells), sustained activation of the STAT1 pathway in hepatocytes, macrophage polarization toward an M1 phenotype and fibrolysis. In contrast, tumor-promoting liver infiltrates are characterized by high content of IFNγ non-producing or interleukin-22 producing lymphocytes, interleukin-6 secretion by various cell types, macrophages with M2 phenotype, sustained STAT3 activation in hepatocytes, fibrogenesis and angiogenesis.
Mentions: We thus propose that the differences between tumor-promoting and tumor-inhibitory liver inflammation may be explained not only by the degree of cytotoxic activity of inflammatory cells, but also by predominance of either STAT1-activating cytokines, such as IFNγ, or STAT3-activating cytokines, such as interleukin-6 or interleukin-22 (Fig. 1). This model is compatible with the finding that the balance of STAT1 and STAT3 activation seems to predict the clinical outcome in cutaneous melanoma.9 During tumor promotion, the presence or absence of IFNγ further influences the tumor microenvironment and tissue remodelling. Indeed, IFNγ is known to promote macrophage polarization toward an M1 phenotype and to inhibit fibrogenesis, whereas M2 macrophages, which are induced by non-IFNγ producing lymphocytes and malignant hepatocytes, promote fibrogenesis and angiogenesis. It is conceivable that the presence of IFNγ during tumor promotion may prevent induction of M2 macrophages. In summary, inflammatory infiltrates with high content of IFNγ-secreting lymphocytes, i.e., Th1 cells, CD8 T cells, some NK cells and some NKT cells, may characterize tumor-suppressive inflammation, whereas infiltrates with high content of IFNγ non-producing or interleukin-22 producing lymphocytes may characterize tumor-promoting infiltrates. Therefore, manipulating the type of chronic inflammation and the composition of tumor-associated inflammatory infiltrates may serve the prevention of cancer.

Bottom Line: Inflammation is a major stimulus for carcinogenesis; however inflammation can also inhibit tumor growth and deplete malignant cells.The differences between cancer-promoting and cancer-inhibitory inflammation are not clear.We identified Interferon-γ as a major mediator of cancer-inhibitory inflammation that promotes anti-cancer immunity in the liver and sensitizes malignant hepatocytes for apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine I; University Medical Centre Hamburg-Eppendorf; Hamburg, Germany.

ABSTRACT
Inflammation is a major stimulus for carcinogenesis; however inflammation can also inhibit tumor growth and deplete malignant cells. The differences between cancer-promoting and cancer-inhibitory inflammation are not clear. We identified Interferon-γ as a major mediator of cancer-inhibitory inflammation that promotes anti-cancer immunity in the liver and sensitizes malignant hepatocytes for apoptosis.

No MeSH data available.


Related in: MedlinePlus