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

著者: Yixuan Zhou, Ingmar N. Bastian, Mark D. Long, Michelle T. Dow, Weihua Li, Tao Liu, Rachael Katie Ngu, Laura Antonucci, Jian Yu Huang, Qui Phung, Xihe Zhao, Sourav Banerjee, Xue-Jia Lin, Hongxia Wang, Brian Dang, Sylvia Choi, Daniel Karin, Hua Su, Mark H. Ellisman, Christina Jamieson, Marcus Bosenberg, Cheng Zhang, Johannes Haybaeck, Lukas Kenner, Kathleen M. Fisch, Richard Bourgon, Genevive Hernandez, Jennie R. Lill, Song Liu, Hannah Carter, Ira Mellman, Michael Karin, Shabnam Shalapour - Proceedings of the National Academy of Sciences, PNAS 2021 被引用: 99

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.