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

• DOI: 10.1073/pnas.2025840118
• Publication Date: 2021-02-19T00:21:21Z
• Authors: Yixuan Zhou; Ingmar Niels Bastian; Mark D. Long; Michelle Dow; Weihua Li; Tao Liu; Rachael Katie Ngu; Laura Antonucci; Jian Yu Huang; Qui T. Phung; Xi-he Zhao; Sourav Banerjee; Xue-Jia Lin; Hongxia Wang; Brian Dang; Sylvia Choi; Daniel Karin; Hua Su; Mark H. Ellisman; Christina Jamieson; Marcus Bosenberg; Zhang Cheng; Johannes Haybaeck; Lukas Kenner; Kathleen M. Fisch; Richard Bourgon; Genevive Hernandez; Jennie R. Lill; Song Liu; Hannah Carter; Ira Mellman; Michael Karin; Shabnam Shalapour
• Keywords: Cross-Presentation; Antigen processing; MHC restriction

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