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         description:Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer1–3, but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes4–6. 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. Deep single-cell RNA sequencing of tumor-infiltrating T cells in non-small-cell lung cancer identifies features associated with functional states and clinical outcome
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      name:Boxi Kang
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Zhouzerui Liu
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Liang Jin
      affiliation:
            name:Peking University Third Hospital
            address:
               name:Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Rui Xing
      affiliation:
            name:Peking University Cancer Hospital & Institute
            address:
               name:Peking University Cancer Hospital & Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Ranran Gao
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Lei Zhang
      affiliation:
            name:Peking University
            address:
               name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Minghui Dong
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xueda Hu
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xianwen Ren
      url:http://orcid.org/0000-0002-8558-5401
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Dennis Kirchhoff
      affiliation:
            name:Bayer AG
            address:
               name:Bayer AG, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Helge Gottfried Roider
      affiliation:
            name:Bayer AG
            address:
               name:Bayer AG, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Tiansheng Yan
      affiliation:
            name:Peking University Third Hospital
            address:
               name:Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Zemin Zhang
      url:http://orcid.org/0000-0003-3789-6536
      affiliation:
            name:Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking University
            address:
               name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
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      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China
      name:Peking University Cancer Hospital & Institute, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Bayer AG, Berlin, Germany
      name:Bayer AG, Berlin, Germany
      name:Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
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