AKT-STAT3 pathway as a downstream target of egfr signaling to regulate PD-l1 expression on NSCLC cells

Sherif Abdelhamed, Keisuke Ogura, Satoru Yokoyama, Ikuo Saiki, Yoshihiro Hayakawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

While cancer development and progression can be controlled by cytotoxic T cells, it is also known that tumor-specific CD8+T cells become functionally impaired by acquiring a group of inhibitory receptors known as immune checkpoints. Amongst those, programmed death-1 (PD-1) is one of the most recognized negative regulators of T cell function. In non-small lung cancers (NSCLCs), the aberrant activation of epidermal growth factor receptor (EGFR) is known to induce PD-L1 expression and further the treatment with gefitinib, a tyrosine kinase inhibitor (TKI) for EGFR, decrease the expression of PD-L1 on NSCLC. Given the acquired resistance to gefitinib treatment frequently observed by developing secondary-site mutations limiting its efficacy, it is important to understand the downstream mechanism of activated-EGFR signaling for regulating PD-L1 in NSCLC. In this study, we demonstrated that AKT-STAT3 pathway could be a potential target for regulating the surface expression of PD-L1 on NSCLCs with aberrant EGFR activity and, further, the inhibition of AKT or STAT3 activity could down-regulate the expression of PD-L1 even in gefitinib-resistant NSCLCs. These results highlight an importance of AKT-STAT3 pathway as a promising target for potentiating anti-tumor immune responses by regulating PD-L1 expression on cancer cells with aberrant EGFR activity.

Original languageEnglish
Pages (from-to)1579-1586
Number of pages8
JournalJournal of Cancer
Volume7
Issue number12
DOIs
StatePublished - 2016

Keywords

  • AKT
  • EGFR
  • Non-small lung cancer
  • PD-L1
  • STAT3

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'AKT-STAT3 pathway as a downstream target of egfr signaling to regulate PD-l1 expression on NSCLC cells'. Together they form a unique fingerprint.

Cite this