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Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing

Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer , but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes . To depict the baseline landscape of the composition, lineage and functional states of tumor... Full description

Journal Title: Nature medicine 2018-07, Vol.24 (7), p.978-985
Main Author: Guo, Xinyi
Other Authors: Zhang, Yuanyuan , Zheng, Liangtao , Zheng, Chunhong , Song, Jintao , Zhang, Qiming , Kang, Boxi , Liu, Zhouzerui , Jin, Liang , Xing, Rui , Gao, Ranran , Zhang, Lei , Dong, Minghui , Hu, Xueda , Ren, Xianwen , Kirchhoff, Dennis , Roider, Helge Gottfried , Yan, Tiansheng , Zhang, Zemin
Format: Electronic Article Electronic Article
Language: English
Subjects:
RNA
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/29942094
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title: Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing
format: Article
creator:
  • Guo, Xinyi
  • Zhang, Yuanyuan
  • Zheng, Liangtao
  • Zheng, Chunhong
  • Song, Jintao
  • Zhang, Qiming
  • Kang, Boxi
  • Liu, Zhouzerui
  • Jin, Liang
  • Xing, Rui
  • Gao, Ranran
  • Zhang, Lei
  • Dong, Minghui
  • Hu, Xueda
  • Ren, Xianwen
  • Kirchhoff, Dennis
  • Roider, Helge Gottfried
  • Yan, Tiansheng
  • Zhang, Zemin
subjects:
  • Adenocarcinoma
  • Antigens
  • Cancer
  • CD8 antigen
  • Cell activation
  • Effector cells
  • Exhaustion
  • Gene expression
  • Gene sequencing
  • Genetic aspects
  • Immunoregulation
  • Interleukin 1
  • Lung cancer
  • Lung cancer, Non-small cell
  • Lymphocytes
  • Lymphocytes T
  • Patients
  • Prognosis
  • Research
  • Ribonucleic acid
  • RNA
  • RNA sequencing
  • T cells
  • Tumors
  • Usage
ispartof: Nature medicine, 2018-07, Vol.24 (7), p.978-985
description: Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer , but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes . To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8 T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleGlobal characterization of T cells in non-small-cell lung cancer by single-cell sequencing
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descriptionCancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer , but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes . To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8 T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.
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subjectAdenocarcinoma ; Antigens ; Cancer ; CD8 antigen ; Cell activation ; Effector cells ; Exhaustion ; Gene expression ; Gene sequencing ; Genetic aspects ; Immunoregulation ; Interleukin 1 ; Lung cancer ; Lung cancer, Non-small cell ; Lymphocytes ; Lymphocytes T ; Patients ; Prognosis ; Research ; Ribonucleic acid ; RNA ; RNA sequencing ; T cells ; Tumors ; Usage
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abstractCancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer , but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes . To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8 T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.
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