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cells, patients, fig, pubmed, cell, article, cancer, mpr, google, scholar, therapy, cas, response, additional, file, expression, immunotherapy, analysis, nmpr, signature, tumor, central, lung, genes, neutrophils, tme, nsclc, singlecell, samples, gene, nat, data, icb, function, combined, treatment, macrophages, immune, zhang, memory, study, phenotype, reported, performed, test, clusters, neoadjuvant, mhcii, expressed, activated,

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lc-ms/ms system analysis multi-subunit ligand-receptor complexes anti-pd-1/anti-ctla-4 combined therapy cn/gsa-human/browse/hra001033 neoadjuvant anti-pd-1/pd-l1 immunotherapy anti-pd-1-treated lung cancers ya han anti-pd-1/pd-l1 therapy tissue expression profiles uhplc-ms/ms lc-ms-grade water viremic hiv-infected subjects small-cell lung cancer single-cell rna sequencing examined single-cell transcriptomes aldo-keto reductase family selected ligand-receptor interactions bd resolve single-cell public scrna-seq data gov/geo/query/acc single-cell mrna quantification estrogen-dependent breast cancer expressed ligand-receptor interactions ap-1/akr1b10 signaling cascade bulk rna-seq data includes bulk rna-seq inferring cell-cell communication single-cell transcriptomic data enhance anti-tumor immunity erk1/2-mapk signalling pathways kaplan–meier survival curve abundant tumor-infiltrating lymphocytes cell-mediated tumor immunity independent rna-seq cohort full size image article download pdf radiation-activated secretory proteins view cell-cell interaction analysis cancer cell-intrinsic expression large-scale expression profiling egfr/alk mutation negative enriched ligand-receptor interactions influences colitis-induced tumorigenesis original author kaplan–meier survival curves results scrna-seq analysis including scrna-seq cohort nonsquamous advanced-stage nsclc anti-tumor immune response

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         headline:Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing
         description:Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance.
         datePublished:2023-03-03T00:00:00Z
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            Systems Biology
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      headline:Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing
      description:Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance.
      datePublished:2023-03-03T00:00:00Z
      dateModified:2023-03-03T00:00:00Z
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      pageEnd:25
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s13073-023-01164-9
      keywords:
         Immunotherapy
         Tumor microenvironment
         Non-small cell lung cancer
         Single cell
         Neutrophil
         Human Genetics
         Metabolomics
         Bioinformatics
         Medicine/Public Health
         general
         Cancer Research
         Systems Biology
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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      name:Tongji University School of Medicine
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         type:PostalAddress
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      address:
         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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         name:Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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      name:Tongji University School of Medicine
      address:
         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
         type:PostalAddress
      name:Tongji University School of Medicine
      address:
         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
         type:PostalAddress
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      address:
         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
         type:PostalAddress
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      address:
         name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
         type:PostalAddress
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      address:
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Person:
      name:Junjie Hu
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            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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      name:Lele Zhang
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            address:
               name:Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Haoran Xia
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Yilv Yan
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Xinsheng Zhu
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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            type:Organization
      name:Fenghuan Sun
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            name:Tongji University School of Medicine
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               type:PostalAddress
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      name:Liangdong Sun
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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      name:Shuangyi Li
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
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      name:Dianke Li
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
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      name:Jin Wang
      affiliation:
            name:Tongji University
            address:
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               type:PostalAddress
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      affiliation:
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            address:
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               type:PostalAddress
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      name:Jing Zhang
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Dongliang Bian
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Huansha Yu
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Yan Chen
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Pengyu Fan
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Qiang Ma
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Gening Jiang
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Chenfei Wang
      affiliation:
            name:Tongji University
            address:
               name:Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Tongji University
            address:
               name:Frontier Science Center for Stem Cells, School of Life Science and Technology, Tongji University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Peng Zhang
      affiliation:
            name:Tongji University School of Medicine
            address:
               name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
            name:The 1st Affiliated Hospital of Wenzhou Medical University
            address:
               name:The 1st School of Medicine, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital of Shihezi University Medical College
            address:
               name:Department of Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
      name:Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
      name:Frontier Science Center for Stem Cells, School of Life Science and Technology, Tongji University, Shanghai, China
      name:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
      name:The 1st School of Medicine, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
      name:Department of Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

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