The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.

ABSTRACT: While immunotherapy has shown some efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation, the AhR, a known but counterintuitive mediator of immunosuppression (interferon (IFN)-γ), and regulation of two immune checkpoints (PD-L1 and IDO). AhR gene-edited LUAD cell lines, a syngeneic LUAD mouse model, bulk and scRNA sequencing of LUADs and tumor-infiltrating T cells were used to map out a signaling pathway leading from IFN-γ through the AhR to JAK/STAT, PD-L1, IDO, and tumor-mediated immunosuppression. The data demonstr

SUBMITTER: Snyder M 

PROVIDER: S-EPMC12213245 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature