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Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer

Author

Listed:
  • Qingzhu Jia

    (Third Military Medical University
    Chongqing Key Laboratory of Tumor Immunotherapy)

  • Wei Wu

    (Third Military Medical University)

  • Yuqi Wang

    (Geneplus-Beijing Institute)

  • Peter B. Alexander

    (Duke University Medical Center)

  • Chengdu Sun

    (Third Military Medical University
    Chongqing Key Laboratory of Tumor Immunotherapy)

  • Zhihua Gong

    (Third Military Medical University
    Chongqing Key Laboratory of Tumor Immunotherapy)

  • Jia-Nan Cheng

    (Third Military Medical University
    Chongqing Key Laboratory of Tumor Immunotherapy
    Third Military Medical University)

  • Huaibo Sun

    (Geneplus-Beijing Institute)

  • Yanfang Guan

    (Geneplus-Beijing Institute)

  • Xuefeng Xia

    (Geneplus-Beijing Institute
    Houston Methodist Research Institute)

  • Ling Yang

    (Geneplus-Beijing Institute)

  • Xin Yi

    (Geneplus-Beijing Institute)

  • Yisong Y. Wan

    (University of North Carolina at Chapel Hill)

  • Haidong Wang

    (Third Military Medical University)

  • Ji He

    (GeneCast Biotechnology Co., Ltd)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

  • Qi-Jing Li

    (Duke University Medical Center
    Third Military Medical University)

  • Bo Zhu

    (Third Military Medical University
    Chongqing Key Laboratory of Tumor Immunotherapy)

Abstract

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.

Suggested Citation

  • Qingzhu Jia & Wei Wu & Yuqi Wang & Peter B. Alexander & Chengdu Sun & Zhihua Gong & Jia-Nan Cheng & Huaibo Sun & Yanfang Guan & Xuefeng Xia & Ling Yang & Xin Yi & Yisong Y. Wan & Haidong Wang & Ji He , 2018. "Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07767-w
    DOI: 10.1038/s41467-018-07767-w
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