Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation

Abstract

Significance T cells recognize their targets via their T-cell receptors (TCRs), which in the case of CD8 + T cells bind to MHC-I:antigen complexes on the surface of target cells. Many cancer cells evade immune recognition and killing by down-regulating MHC-I AgPPM. Here, we show how the histone acetyl transferases p300/CBP together with NF-κB epigenetically regulate expression of MHC-I molecules, immunoproteasome subunits, and peptide transporter to enable proper MHC-I antigen presentation. Notably, this pathway is frequently disrupted in human cancers. We now show that certain chemotherapeutics can augment MHC-I antigen presentation via NF-κB and p300/CBP activation, thereby enhancing cancer cell recognition and killing by effector CD8 + CTLs.