dc.contributor.author | Wennerberg, E | |
dc.contributor.author | Mukherjee, S | |
dc.contributor.author | Spada, S | |
dc.contributor.author | Hung, C | |
dc.contributor.author | Agrusa, CJ | |
dc.contributor.author | Chen, C | |
dc.contributor.author | Valeta-Magara, A | |
dc.contributor.author | Rudqvist, N-P | |
dc.contributor.author | Van Nest, SJ | |
dc.contributor.author | Kamel, MK | |
dc.contributor.author | Nasar, A | |
dc.contributor.author | Narula, N | |
dc.contributor.author | Mittal, V | |
dc.contributor.author | Markowitz, GJ | |
dc.contributor.author | Zhou, XK | |
dc.contributor.author | Adusumilli, PS | |
dc.contributor.author | Borczuk, AC | |
dc.contributor.author | White, TE | |
dc.contributor.author | Khan, AG | |
dc.contributor.author | Balderes, PJ | |
dc.contributor.author | Lorenz, IC | |
dc.contributor.author | Altorki, N | |
dc.contributor.author | Demaria, S | |
dc.contributor.author | McGraw, TE | |
dc.contributor.author | Stiles, BM | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-06-20T08:19:24Z | |
dc.date.available | 2022-06-20T08:19:24Z | |
dc.date.issued | 2022-03-16 | |
dc.identifier | ARTN eabe8195 | |
dc.identifier.citation | Science Translational Medicine, 2022, 14 (636), pp. eabe8195 - | en_US |
dc.identifier.issn | 1946-6234 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5185 | |
dc.identifier.eissn | 1946-6242 | |
dc.identifier.eissn | 1946-6242 | |
dc.identifier.doi | 10.1126/scitranslmed.abe8195 | |
dc.description.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 blockade of the NAD+-degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell-dependent manner. This was associated with increased infiltration of activated P2X7R+CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies. | |
dc.format | Print-Electronic | |
dc.format.extent | eabe8195 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | en_US |
dc.relation.ispartof | Science Translational Medicine | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_US |
dc.subject | ADP Ribose Transferases | |
dc.subject | Adenosine Diphosphate | |
dc.subject | Animals | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | GPI-Linked Proteins | |
dc.subject | Humans | |
dc.subject | Lung Neoplasms | |
dc.subject | Mice | |
dc.subject | T-Lymphocyte Subsets | |
dc.title | Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-02-22 | |
dc.date.updated | 2022-06-17T14:03:06Z | |
rioxxterms.version | AM | en_US |
rioxxterms.versionofrecord | 10.1126/scitranslmed.abe8195 | en_US |
rioxxterms.licenseref.startdate | 2022-03-16 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35294260 | |
pubs.issue | 636 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiation-enhanced Immunotherapy | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published | |
pubs.volume | 14 | |
icr.researchteam | Radiation Immunotherapy | en_US |
dc.contributor.icrauthor | Wennerberg, Erik | |