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nature portfolio privacy policy immune editing tailed mann–whitney u-test computational genomics tools intratumoral regional variation medical research anti-human cd33-apc/cy7 advertising pre-primed cytotoxic t-lymphocyte qi-jing li anti-pd-l1 antibody mpdl3280a anti-human hla-dr-pe pre-existing anti-tumor reactivity io/picard/ social media supplementary data small-cell lung cancer jia-nan cheng rna-seq libraries high-quality paired-end reads antigen-specific t-cell receptors t-cell-inflamed tumor microenvironment reprints supplementary information anti-pd-1/pd-l1 treatment paired single-cell analyses development library selection schemes systemic nature dominant t-cell clones local t-cell expansion functional nature anti-human cd14-apc cd8+ t-cell infiltration11 t-cell repertoire clonality8 measuring anti-tumor reactivity anti-human cd45-pacificblue anti-human cd3-fitc diversified t-cell clonotypes unlike t-cell activation anti-human cd8-percp cd8+ t-cell infiltration transcriptomic expression data intratumoral t-cell repertoires anti-pd-l1 treatment4 boost cd52-mediated cd8+ fluorescence-activated cell sorter rna profiling data org/cancer/cga/mutect

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         headline:Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer
         description:Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy. Intratumoral immunity heterogeneity is poorly characterized. Here the authors apply exome sequencing, transcriptome profiling and T-cell repertoire profiling to multiple loci of non-small-cell lung cancer patients' biopsies and find high spatial immune heterogeneity with local mutational burden correlating with T-cell clonal expansion but not with cytotoxicity.
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            name:Chongqing Key Laboratory of Tumor Immunotherapy
            address:
               name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Wei Wu
      affiliation:
            name:Third Military Medical University
            address:
               name:Department of Cardiothorathic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Yuqi Wang
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Peter B. Alexander
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Immunology, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Chengdu Sun
      affiliation:
            name:Third Military Medical University
            address:
               name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
            name:Chongqing Key Laboratory of Tumor Immunotherapy
            address:
               name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Zhihua Gong
      affiliation:
            name:Third Military Medical University
            address:
               name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
            name:Chongqing Key Laboratory of Tumor Immunotherapy
            address:
               name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Jia-Nan Cheng
      affiliation:
            name:Third Military Medical University
            address:
               name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
            name:Chongqing Key Laboratory of Tumor Immunotherapy
            address:
               name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
               type:PostalAddress
            type:Organization
            name:Third Military Medical University
            address:
               name:Biomedical Analysis Center, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Huaibo Sun
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Yanfang Guan
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xuefeng Xia
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
            name:Houston Methodist Research Institute
            address:
               name:Houston Methodist Research Institute, Houston, USA
               type:PostalAddress
            type:Organization
      name:Ling Yang
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xin Yi
      affiliation:
            name:Geneplus-Beijing Institute
            address:
               name:Geneplus-Beijing Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Yisong Y. Wan
      affiliation:
            name:University of North Carolina at Chapel Hill
            address:
               name:Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
               type:PostalAddress
            type:Organization
      name:Haidong Wang
      affiliation:
            name:Third Military Medical University
            address:
               name:Department of Cardiothorathic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Ji He
      affiliation:
            name:GeneCast Biotechnology Co., Ltd
            address:
               name:GeneCast Biotechnology Co., Ltd, Beijing, China
               type:PostalAddress
            type:Organization
      name:P. Andrew Futreal
      affiliation:
            name:The University of Texas MD Anderson Cancer Center
            address:
               name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
               type:PostalAddress
            type:Organization
      name:Qi-Jing Li
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Immunology, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:Third Military Medical University
            address:
               name:Biomedical Analysis Center, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Bo Zhu
      affiliation:
            name:Third Military Medical University
            address:
               name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
            name:Chongqing Key Laboratory of Tumor Immunotherapy
            address:
               name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
      name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
      name:Department of Cardiothorathic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
      name:Geneplus-Beijing Institute, Beijing, China
      name:Department of Immunology, Duke University Medical Center, Durham, USA
      name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
      name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
      name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
      name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
      name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
      name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China
      name:Biomedical Analysis Center, Third Military Medical University, Chongqing, China
      name:Geneplus-Beijing Institute, Beijing, China
      name:Geneplus-Beijing Institute, Beijing, China
      name:Geneplus-Beijing Institute, Beijing, China
      name:Houston Methodist Research Institute, Houston, USA
      name:Geneplus-Beijing Institute, Beijing, China
      name:Geneplus-Beijing Institute, Beijing, China
      name:Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
      name:Department of Cardiothorathic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
      name:GeneCast Biotechnology Co., Ltd, Beijing, China
      name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
      name:Department of Immunology, Duke University Medical Center, Durham, USA
      name:Biomedical Analysis Center, Third Military Medical University, Chongqing, China
      name:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
      name:Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, China

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