Tofacitinib overcomes an IFNγ-induced decrease in NK cell-mediated cytotoxicity via the regulation of immune-related molecules in LC-2/ad.

ABSTRACT:

Background

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with nonsmall cell lung cancer (NSCLC). One major PD-L1 inducer is IFNγ, which is secreted by T cells and NK cells. Importantly, IFNγ-induced PD-L1 is one of the major mechanisms by which cancer cells escape host immunity.

Methods

Here, we found that the NSCLC cell line, LC-2/ad, has a unique character; the PD-L1 expression in these cells is up-regulated by both IFNγ and epidermal growth factor (EGF).

Results

Comparative analysis of the cell signaling pathway showed that IFNγ activates STAT1 signaling, while EGF activates AKT, MAPK, and ribosomal protein S6 kinase in LC-2/ad cells. IFNγ-induced PD-L1, but not EGF-indu

SUBMITTER: Okita R 

PROVIDER: S-EPMC7952785 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature