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Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing

Author

Listed:
  • Cornelius H. L. Kürten

    (University Hospital Essen, University Duisburg-Essen
    University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Aditi Kulkarni

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Anthony R. Cillo

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Patricia M. Santos

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Anna K. Roble

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Sayali Onkar

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh
    University of Pittsburgh School of Medicine)

  • Carly Reeder

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Stephan Lang

    (University Hospital Essen, University Duisburg-Essen)

  • Xueer Chen

    (University of Pittsburgh)

  • Umamaheswar Duvvuri

    (University of Pittsburgh)

  • Seungwon Kim

    (University of Pittsburgh)

  • Angen Liu

    (University of Pittsburgh
    University of Pittsburgh)

  • Tracy Tabib

    (University of Pittsburgh)

  • Robert Lafyatis

    (University of Pittsburgh)

  • Jian Feng

    (University of Pittsburgh
    University of Pittsburgh
    Cancer Virology Program, UPMC Hillman Cancer Center)

  • Shou-Jiang Gao

    (University of Pittsburgh
    University of Pittsburgh
    Cancer Virology Program, UPMC Hillman Cancer Center)

  • Tullia C. Bruno

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Dario A. A. Vignali

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Xinghua Lu

    (University of Pittsburgh)

  • Riyue Bao

    (University of Pittsburgh
    University of Pittsburgh)

  • Lazar Vujanovic

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh)

  • Robert L. Ferris

    (University of Pittsburgh
    Tumor Microenvironment Center, UPMC Hillman Cancer Center
    University of Pittsburgh
    University of Pittsburgh)

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)+ and 12 HPV– HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV+ TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.

Suggested Citation

  • Cornelius H. L. Kürten & Aditi Kulkarni & Anthony R. Cillo & Patricia M. Santos & Anna K. Roble & Sayali Onkar & Carly Reeder & Stephan Lang & Xueer Chen & Umamaheswar Duvvuri & Seungwon Kim & Angen L, 2021. "Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27619-4
    DOI: 10.1038/s41467-021-27619-4
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