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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
- Source :
- Nature medicine, Nature medicine, vol. 24, no. 7, pp. 994-1004, Nature Medicine
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
Transcription, Genetic
medicine.medical_treatment
T cell
Programmed Cell Death 1 Receptor
610 Medicine & health
Biology
CD8-Positive T-Lymphocytes
NSCLC
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
0302 clinical medicine
Immune system
Lymphocytes, Tumor-Infiltrating
1300 General Biochemistry, Genetics and Molecular Biology
T-Lymphocyte Subsets
10049 Institute of Pathology and Molecular Pathology
Carcinoma, Non-Small-Cell Lung
medicine
Cytotoxic T cell
Humans
Lung cancer
T cell exhaustion
chemokine
General Medicine
T lymphocyte
Immunotherapy
CXCL13
immune checkpoint blockade
medicine.disease
Lipid Metabolism
Chemokine CXCL13
3. Good health
Mitochondria
Gene Expression Regulation, Neoplastic
030104 developmental biology
Cytokine
medicine.anatomical_structure
Glucose
Phenotype
Virus Diseases
030220 oncology & carcinogenesis
IL-10
Chronic Disease
Cancer research
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
Glucose/metabolism
Lung Neoplasms/genetics
Lung Neoplasms/immunology
Lymphocytes, Tumor-Infiltrating/immunology
Mitochondria/metabolism
Mitochondria/ultrastructure
Programmed Cell Death 1 Receptor/metabolism
T-Lymphocyte Subsets/immunology
Virus Diseases/immunology
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 1546170X and 10788956
- Volume :
- 24
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....80a11afb8d7bbc106488bcd31ac01e17