Regulation of the translation activity of antigen-specific mRNA is responsible for antigen loss and tumor immune escape in a HER2-expressing tumor model

Scientific Reports
Baek-Sang HanJeong-Im Sin

Abstract

Tumor cells tend to behave differently in response to immune selective conditions. Contrary to those in therapeutic antitumor conditions, tumor cells in prophylactic antitumor conditions lose antigen expression for antitumor immune escape. Here, using a CT26/HER2 tumor model, we investigate the underlying mechanism(s). We selected tumor cell variants (CT26/HER2-A1 and -A2) displaying resistance to antitumor protective immunity and loss of HER2 antigen expression. These immune-resistant cells failed to induce Ag-specific IgG and IFN-γ responses while forming tumors at the same rate as CT26/HER2 cells. RT-PCR, qRT-PCR, PCR, Western blot and DNA sequencing analyses demonstrated that HER2 expression was inhibited at the post-transcriptional level in these immune-resistant cells, suggesting that tumor cells may escape antitumor immunity through the post-transcriptional regulation of antigen gene expression. The proteasome and lysosomal protein degradation pathways were not responsible for antigen loss, as determined by an inhibitor assay. Finally, HER2 mRNA was found to be not present in the monosomes and polysomes of CT26/HER2-A2 cells, as opposed to CT26/HER2 cells, suggesting that the translation activity of HER2 mRNAs may be sup...Continue Reading

References

Mar 15, 1990·International Journal of Cancer. Journal International Du Cancer·P G NataliA Ullrich
Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·G E PeoplesT J Eberlein
Sep 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·J P MedemaR Offringa
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 24, 2003·The Journal of Molecular Diagnostics : JMD·Alison MillsonElaine Lyon
Apr 27, 2005·Nature Reviews. Molecular Cell Biology·V Narry Kim
Feb 13, 2007·Current Opinion in Immunology·Jack D Bui, Robert D Schreiber
Mar 18, 2008·FEBS Letters·Tina GlisovicGideon Dreyfuss
Jun 10, 2010·Nature Reviews. Molecular Cell Biology·Mikko TaipaleSusan Lindquist
Aug 9, 2011·Nature Reviews. Cancer·Marieke van KouwenhoveReuven Agami
Aug 24, 2013·International Journal of Molecular Sciences·Hoin KangEun Kyung Lee
Oct 9, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Trevor E AngellAlan L Epstein
Apr 23, 2015·Human Vaccines & Immunotherapeutics·Sang-Yeul Lee, Jeong-Im Sin
Oct 27, 2015·Scientific Reports·Chiao-Wen KangChun-Yen Lin

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Citations

Apr 25, 2020·Cancers·Veronica Mendoza-ReinosoPierrick G J Fournier
Jul 20, 2021·Frontiers in Immunology·Alexander J StephensShisong Jiang

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Methods Mentioned

BETA
ELISA
PCR
flow cytometry
transgenic
enzyme-linked immunosorbent assay
electrophoresis
Fluorescence-activated cell sorting

Software Mentioned

SPSS
Excel

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