Phosphoinositide 3-kinase signaling can modulate MHC Class i and II expression

Sanjay Chandrasekaran, Maiko Sasaki, Christopher D. Scharer, Haydn T. Kissick, Dillon G. Patterson, Kelly R. Magliocca, John T. Seykora, Bishu Sapkota, David A. Gutman, Lee A. Cooper, Gregory B. Lesinski, Edmund K. Waller, Susan N. Thomas, Sergei V. Kotenko, Jeremy M. Boss, Carlos S. Moreno, Robert A. Swerlick, Brian P. Pollack*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Molecular events activating the PI3K pathway are frequently detected in human tumors and the activation of PI3K signaling alters numerous cellular processes including tumor cell proliferation, survival, and motility. More recent studies have highlighted the impact of PI3K signaling on the cellular response to interferons and other immunologic processes relevant to antitumor immunity. Given the ability of IFNγ to regulate antigen processing and presentation and the pivotal role of MHC class I (MHCI) and II (MHCII) expression in T-cell-mediated antitumor immunity, we sought to determine the impact of PI3K signaling on MHCI and MHCII induction by IFNγ.We found that the induction of cell surface MHCI and MHCII molecules by IFNγ is enhanced by the clinical grade PI3K inhibitors dactolisib and pictilisib. We also found that PI3K inhibition increases STAT1 protein levels following IFNγ treatment and increases accessibility at genomic STAT1-binding motifs. Conversely, we found that pharmacologic activation of PI3K signaling can repress the induction of MHCI and MHCII molecules by IFNγ, and likewise, the loss of PTEN attenuates the induction of MHCI, MHCII, and STAT1 by IFNγ. Consistent with these in vitro studies, we found that within human head and neck squamous cell carcinomas, intratumoral regions with high phospho-AKT IHC staining had reduced MHCI IHC staining.

Original languageEnglish (US)
Pages (from-to)2395-2409
Number of pages15
JournalMolecular Cancer Research
Volume17
Issue number12
DOIs
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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