Targeting the NAT10/NPM1 axis abrogates PD-L1 expression and improves the response to immune checkpoint blockade therapy.

ABSTRACT:

Background

PD-1/PD-L1 play a crucial role as immune checkpoint inhibitors in various types of cancer. Although our previous study revealed that NPM1 was a novel transcriptional regulator of PD-L1 and stimulated the transcription of PD-L1, the underlying regulatory mechanism remains incompletely characterized.

Methods

Various human cancer cell lines were used to validate the role of NPM1 in regulating the transcription of PD-L1. The acetyltransferase NAT10 was identified as a facilitator of NPM1 acetylation by coimmunoprecipitation and mass spectrometry. The potential application of combined NAT10 inhibitor and anti-CTLA4 treatment was evaluated by an animal model.

Results

We demonstrated that NPM1 enhanced the transcription of PD-L1 in various types of cancer, and the

SUBMITTER: Qin G 

PROVIDER: S-EPMC10799409 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature