A transcriptionally and functionally distinct PD-1<sup>+</sup> CD8<sup>+</sup> T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.

Details

Serval ID
serval:BIB_D581A7793334
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A transcriptionally and functionally distinct PD-1<sup>+</sup> CD8<sup>+</sup> T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.
Journal
Nature medicine
Author(s)
Thommen D.S., Koelzer V.H., Herzig P., Roller A., Trefny M., Dimeloe S., Kiialainen A., Hanhart J., Schill C., Hess C., Savic Prince S., Wiese M., Lardinois D., Ho P.C., Klein C., Karanikas V., Mertz K.D., Schumacher T.N., Zippelius A.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
24
Number
7
Pages
994-1004
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Evidence from mouse chronic viral infection models suggests that CD8 <sup>+</sup> T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8 <sup>+</sup> T lymphocyte populations with high (PD-1 <sup>T</sup> ), intermediate (PD-1 <sup>N</sup> ) and no PD-1 expression (PD-1 <sup>-</sup> ) from non-small-cell lung cancer patients. PD-1 <sup>T</sup> T cells showed a markedly different transcriptional and metabolic profile from PD-1 <sup>N</sup> and PD-1 <sup>-</sup> lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1 <sup>T</sup> lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1 <sup>T</sup> cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention.
Keywords
CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/ultrastructure, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/immunology, Chemokine CXCL13/metabolism, Chronic Disease, Gene Expression Regulation, Neoplastic, Glucose/metabolism, Humans, Lipid Metabolism, Lung Neoplasms/genetics, Lung Neoplasms/immunology, Lymphocytes, Tumor-Infiltrating/immunology, Mitochondria/metabolism, Mitochondria/ultrastructure, Phenotype, Programmed Cell Death 1 Receptor/metabolism, T-Lymphocyte Subsets/immunology, Transcription, Genetic, Virus Diseases/immunology
Pubmed
Web of science
Create date
25/06/2018 11:20
Last modification date
20/08/2019 16:55
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