A novel approach to rescue immune escape in oral squamous cell carcinoma: Combined use of interferon-γ and LY294002.
Major histocompatibility complex (MHC) class I molecules have been found to be downmodulated in many tumors. The antigen-processing machinery (APM) genes, especially transporters associated with antigen processing (TAP)-1 and tapasin play important roles in the processing of class I antigens. In this study, we investigated the expression of TAP-1 and tapasin in oral squamous cell carcinoma (OSCC); the result indicated significant down-regulation in the expression of these genes. Interferon (IFN)-γ treatment was applied. After the addition of IFN-γ, unexpectedly, the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was activated, which induced the proliferation of tumor cells. With the combined application of LY294002 (specific inhibitor of AKT signaling) and IFN-γ, tumor cell apoptosis was induced and the expression of TAP-1 and tapasin was still up-regulated. Hence, our method is a novel and efficient approach to use IFN-γ for rescuing the cells from immunosurveillance.
Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, P.R. China.
Wei
W
Han
Hongya
H
Pan
Linlin
L
Jiang
Kuijie
K
Wei
Duohong
D
Zou
Zhiyuan
Z
Zhang
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019139:Tumor Escape / Q000187:drug effects*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002867:Chromones; D026901:Membrane Transport Proteins; D009025:Morpholines; D012333:RNA, Messenger; C073119:TAP1 protein, human; C107762:tapasin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007371:Interferon-gamma