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Forum on Immunopathological Diseases and Therapeutics
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN Imprimir: 2151-8017
ISSN On-line: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v1.i1-2.20
pages 17-30

Yin Yang 1 Is a Tumor Immune-Suppressor Gene Product

Stavroula Baritaki
Department of Microbiology and Molecular Genetics, David Geffen School of Medicine, Jonnson Comprehensive Cancer Center, University of California(UCLA), USA

RESUMO

Cancer patients initially respond to conventional therapies; however, a subset does not initially respond and others fail to respond to additional therapies. The mechanisms underlying resistance are not completely elucidated. We have identified Yin Yang 1 (YY1) as a pivotal regulator of tumor cell resistance to apoptosis by immunotherapeutics. YY1 has been shown to negatively regulate the transcription and expression of the TNF family receptors Fas and DR5, and maintains resistance to corresponding ligands, FasL and TRAIL, respectively. YY1 inhibition results in the upregulation of Fas and DR5 expression and sensitiza-tion to apoptosis. We have demonstrated the direct role of YY1 in the regulation of immune resistance, namely, reversal of resistance through inhibition of NF-κB activity, S-nitrosylation of YY1, and siRNA YY1. We have reported that treatment of immune-resistant tumor cells by various agents, such as chemotherapeutic drugs, proteasome inhibitors, the NF-κB inhibitor DHMEQ, and rituximab, all resulted in the inhibition of YY1 and sensitization to immunotherapy. Many tumors overexpress YY1, and YY1 levels correlate with tumor progression and are of bad prognostic significance. We introduce YY1 as a novel tumor immune-suppressor gene product and therefore inhibition of YY1 could be a novel approach to reverse tumor cell resistance to immunotherapy.


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