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STAT3 and immune escape in head and neck squamous cell carcinoma
Author(s) -
Leibowitz Michael Shinichi,
LopezAlbaitero Andres,
Ferris Robert L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.23
Subject(s) - downregulation and upregulation , ctl* , stat protein , immune system , stat3 , cancer research , cytotoxic t cell , head and neck squamous cell carcinoma , biology , stat1 , antigen , immunology , signal transduction , microbiology and biotechnology , cd8 , cancer , head and neck cancer , gene , biochemistry , genetics , in vitro
One strategy of immune escape involves downregulation of the antigen processing machinery (APM), enabling tumor cell evasion by cytotoxic T lymphocytes (CTL), however the mechanism responsible for this has not been determined. Previous work in our and other laboratories has shown that cell lines and tissues derived from HNSCC downregulate APM components such as transporter associated with antigen processing (TAP)‐1 and TAP2. Treatment with IFN‐γ upregulates APM components, and restores the ability of tumor antigen‐specific CTL to recognize and lyse these tumor cell lines. HNSCC tumors overexpress signal transducer and activator of transcription (STAT)‐3, a transcription factor activated by interleukin‐6 (IL‐6). Pre‐treatment of HNSCC cell lines with IL‐6 abrogates IFN‐γ mediated STAT1 activation, suggesting that STAT3 negatively regulates STAT1 activation. Thus, we hypothesized that overexpression of STAT3 in HNSCC may contribute to downregulation of APM components and CTL recognition by decreasing STAT1 activity, thereby contributing to immune escape. Preliminary studies indicate that IL‐6 pre‐treatment can decrease IFN‐γ mediated upregulation of APM components at both the transcriptional and translational level. Investigation is underway to elucidate the interaction of STAT1 and STAT3, and their potential contribution to APM component mediated tumor immune escape from CTL recognition.