biostudies-literatureWennerberg ENCI NIH HHSeabe8195https://www.ebi.ac.uk/biostudies/studies/S-EPMC9256502biostudies-literatureUnknown14(636)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 bScience translational medicineExpression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.PMC9256502R01 CA198533P30 CA008748Lorenz ICAdusumilli PSHung CWennerberg EKamel MKRudqvist NPVan Nest SJMarkowitz GJMcGraw TEDemaria SValeta-Magara AWhite TEZhou XKKhan AGBalderes PJBorczuk ACChen CAltorki NStiles BMMittal VAgrusa CJMukherjee SNarula NNasar ASpada SfalseExpression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.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 b2022-01-01T00:00:00Z2022 Mar2025-05-29T19:36:41.589Z2024-11-06T07:25:03.791ZS-EPMC92565023529426010.1126/scitranslmed.abe8195