Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.

ABSTRACT: Most patients with non-small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)-induced cell death (NICD) of P2X7 receptor (P2X7R)-expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono-adenosine 5'-diphosphate (ADP)-ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R⁺ CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R⁺ CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon b

SUBMITTER: Wennerberg E 

PROVIDER: S-EPMC9256502 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature