API5 confers tumoral immune escape through FGF2-dependent cell survival pathway

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Title
API5 confers tumoral immune escape through FGF2-dependent cell survival pathway
Author(s)
Kyung Hee Noh; Seok Ho Kim; J H Kim; K H Song; Y H Lee; T H Kang; H D Han; A K Sood; J Ng; K Kim; C H Sonn; V Kumar; C Yee; K M Lee; T W Kim
Bibliographic Citation
Cancer Research, vol. 74, no. 13, pp. 3556-3566
Publication Year
2014
Abstract
Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to immunotherapies to which they are otherwise resistant. In this study, we show that the antiapoptotic gene API5 acts as an immune escape gene in tumors by rendering them resistant to apoptosis triggered by tumor antigen-specificT cells. Its RNAi-mediated silencing in tumor cells expressing high levels of API5 restored antigen-specific immune sensitivity. Conversely, introducing API5 into API5low cells conferred immune resistance. Mechanistic investigations revealed that API5 mediated resistance by upregulating FGF2 signaling through a FGFR1/PKCd/ERK effector pathway that triggered degradation of the proapoptotic molecule BIM. Blockade of FGF2, PKCd, or ERK phenocopied the effect of API5 silencing in tumor cells expressing high levels of API5 to either murine or human antigen-specific T cells. Our results identify a novel mechanism of immune escape that can be inhibited to potentiate the efficacy of targeted active immunotherapies. Cancer Res; 74(13); 3556-66.
ISSN
0008-5472
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/0008-5472.CAN-13-3225
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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