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Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing

Author

Listed:
  • Sijia Cui

    (Second Affiliated Hospital of Wenzhou Medical University
    Baylor College of Medicine)

  • Nicholas McGranahan

    (University College London)

  • Jing Gao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Peng Chen

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wei Jiang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lingrong Yang

    (Hangzhou Cancer Hospital)

  • Li Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Junfang Liao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Tian Xie

    (Hangzhou Normal University)

  • Congying Xie

    (Second Affiliated Hospital of Wenzhou Medical University)

  • Tariq Enver

    (University College London)

  • Shixiu Wu

    (Second Affiliated Hospital of Wenzhou Medical University
    Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, it is discovered that genomic, epigenomic, and transcriptomic ITH are underpinned by ongoing chromosomal instability. Based on the RNA-seq data, we observe diverse levels of immune infiltrate across different tumor sites from the same tumor. We reveal genetic mechanisms of neoantigen evasion under distinct selection pressure from the diverse immune microenvironment. Overall, our work offers an avenue of dissecting the complex contribution of the multi-omics level to the ITH in ESCC and thereby enhances the development of clinical therapy.

Suggested Citation

  • Sijia Cui & Nicholas McGranahan & Jing Gao & Peng Chen & Wei Jiang & Lingrong Yang & Li Ma & Junfang Liao & Tian Xie & Congying Xie & Tariq Enver & Shixiu Wu, 2023. "Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36558-1
    DOI: 10.1038/s41467-023-36558-1
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