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 a...
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Published in | Nature medicine Vol. 24; no. 7; pp. 994 - 1004 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.07.2018
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. PD-1
T
T cells showed a markedly different transcriptional and metabolic profile from PD-1
N
and PD-1
–
lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1
T
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
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 potential avenues for therapeutic intervention.
Tumor-infiltrating CD8
+
T cells with high expression of PD-1 in non-small-cell lung cancer are distinct from exhausted T cells in chronic virus infection, have high tumor reactivity and associate with response to PD-1-targeted immunotherapy. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors jointly directed this work. |
ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/s41591-018-0057-z |