Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression.

Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression. Research Abstract Details 

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Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression. Abstract Text:

Dafeng Yang,Trina J Stewart,Kimberly K Smith,David Georgi,Scott I Abrams,Kebin Liu,Dafeng Yang,Trina J Stewart,Kimberly K Smith,David Georgi,Scott I Abrams,Kebin Liu,

The host immune system functions as an intrinsic surveillance network in the recognition and destruction of tumor cells, and it has been demonstrated that lymphocytes and IFN-gamma are the primary tumor suppressors of the immune system. However, the immune system can concurrently select for tumor variants with reduced immunogenicity and aggressive phenotypes. We report here that tumor escape variants that have survived CTL adoptive immunotherapy exhibited decreased expression levels of both Fas and IFN-gammaR in vitro. Furthermore, examination of spontaneously arising mouse primary mammary carcinoma and lung metastases revealed that both Fas and IFN-gammaR protein levels were dramatically lower in lung metastases than in primary tumors in vivo. Functional disruption of either the Fas- or the IFN-gamma signaling pathway enhanced the colonization efficiency of preexisting metastatic tumor cells, whereas disruption of both Fas and IFN-gammaR pathways resulted in synergistic augmentation of the colonization efficiency of the preexisting metastatic tumor cells, as determined by experimental lung metastases assay. Gene expression profiling revealed that altered expression of genes involved in immediate IFN-gammaR signaling, the interferon primary response, apoptosis and tumor colonization is associated with loss of IFN-gammaR function and enhanced metastatic potential. Interestingly, disruption of IFN-gammaR function did not alter tumor cell susceptibility to CTL-mediated cytotoxicity, but is linked to enhanced infiltration of endogenous T cells in the tumor microenvironment in vivo. These findings suggest that coordinate downregulation of Fas and IFN-gammaR, 2 key components of cancer immunosurveillance system on tumor cells, leads to a more aggressive metastatic phenotype.

Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression. Publishing Authors By Initials

D Yang,TJ Stewart,KK Smith,D Georgi,SI Abrams,K Liu,D Yang,TJ Stewart,KK Smith,D Georgi,SI Abrams,K Liu,

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Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: International journal of cancer. Journal internati

VOLUME: 122

Page Numbers: 350-62

Journal Abbreviation: Int. J. Cancer

ISSN: 1097-0215

DAY: 15

MONTH: Jan

YEAR: 2008

Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression. Information

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LANGUAGE: eng

NlmUniqueID: 42124

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Grant and Affiliation Information for Downregulation of IFN-gammaR in association with loss of Fas function is linked to tumor progression.

AFFILIATION: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA.

Country: United States

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MEDLINETA: Int J Cancer

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