NLRC5/MHC class I transactivator is a target for immune evasion in cancer | Academic Article individual record
abstract

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as \"NLRC5\" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

author list (cited authors)
Yoshihama, S., Roszik, J., Downs, I., Meissner, T. B., Vijayan, S., Chapuy, B., ... Kobayashi, K. S.
publication date
2016
keywords
  • Antigen Peptide Transporter-1Antigen PresentationBiomarkers, TumorCD8-Positive T-LymphocytesCysteine EndopeptidasesFemaleGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansIntracellular Signaling Peptides And ProteinsMaleNeoplasm ProteinsNeoplasmsProteasome Endopeptidase ComplexTrans-ActivatorsTranscriptional ActivationTumor EscapeBeta 2-MicroglobulinMHC Class ICITACancerImmune EvasionNLRC5