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A transcriptionally and functionally distinct PD-1(+) CD8(+) T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade

Evidence from mouse chronic viral infection models suggests that CD8(+) 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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110381/
https://www.ncbi.nlm.nih.gov/pubmed/29892065
http://dx.doi.org/10.1038/s41591-018-0057-z
Descripción
Sumario:Evidence from mouse chronic viral infection models suggests that CD8(+) 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(+) T lymphocyte populations with high (PD-1(T)), intermediate (PD-1(N)) and no PD-1 expression (PD-1(-)) from non-small cell lung cancer patients. We observed that, PD-1(T) T cells show a markedly different transcriptional and metabolic profile as compared to PD-1(N) and PD-1(-) lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1(T) lymphocytes are impaired in classical effector cytokine production, they produce CXCL13 that mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1(T) 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 novel potential avenues for therapeutic intervention.