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Data from Association of IFN-γ Signal Transduction Defects with Impaired HLA Class I Antigen Processing in Melanoma Cell Lines
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Data from Association of IFN-γ Signal Transduction Defects with Impaired HLA Class I Antigen Processing in Melanoma Cell Lines
Data from Association of IFN-γ Signal Transduction Defects with Impaired HLA Class I Antigen Processing in Melanoma Cell Lines
AR
Annedore Respa
Annedore Respa
JB
Juergen Bukur
Juergen Bukur
SF
Soldano Ferrone
Soldano Ferrone
GP
Graham Pawelec
Graham Pawelec
YZ
Yingdong Zhao
Yingdong Zhao
EW
Ena Wang
Ena Wang
FM
Francesco M. Marincola
Francesco M. Marincola
BS
Barbara Seliger
Barbara Seliger
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6518948.v1
Abstract
Purpose: Abnormalities in the constitutive and IFN-γ–inducible HLA class I surface antigen expression of tumor cells is often associated with an impaired expression of components of the antigen processing machinery (APM). Hence, we analyzed whether there exists a link between the IFN-γ signaling pathway, constitutive HLA class I APM component expression, and IFN-γ resistance.Experimental Design: The basal and IFN-γ–inducible expression profiles of HLA class I APM and IFN-γ signal transduction cascade components were assessed in melanoma cells by real-time PCR (RT-PCR), Western blot analysis and/or flow cytometry, the integrity of the Janus activated kinase (JAK) 2 locus by comparative genomic hybridization. JAK2 was transiently overexpressed in JAK2− cells. The effect of IFN-γ on the cell growth was assessed by XTT [2,3-bis(2-methoxy-4-nitro-S-sulfophenynl)-H-tetrazolium-5-carboxanilide inner salt] assay.Results: The analysis of 8 melanoma cell lines linked the IFN-γ unresponsiveness of Colo 857 cells determined by lack of inducibility of HLA class I surface expression on IFN-γ treatment to a deletion of JAK2 on chromosome 9, whereas other IFN-γ signaling pathway components were not affected. In addition, the constitutive HLA class I APM component expression levels were significantly reduced in JAK2− cells. Furthermore, JAK2-deficient cells were also resistant to the antiproliferative effect of IFN-γ. Transfection of wild-type JAK2 into JAK2− Colo 857 not only increased the basal APM expression but also restored their IFN-γ sensitivity.Conclusions: Impaired JAK2 expression in melanoma cells leads to reduced basal expression of MHC class I APM components and impairs their IFN-γ inducibility, suggesting that malfunctional IFN-γ signaling might cause HLA class I abnormalities. Clin Cancer Res; 17(9); 2668–78. ©2011 AACR.
Keywords
ANTIGEN
IFN Γ
HLA
CLASS I APM COMPONENT
BASAL
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