Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer.
Anthony R Cillo, Cornelius H L Kürten, Tracy Tabib, Zengbiao Qi, Sayali Onkar, Ting Wang, Angen Liu, Umamaheswar Duvvuri, Seungwon Kim, Ryan J Soose, Steffi Oesterreich, Wei Chen, Robert Lafyatis, Tullia C Bruno, Robert L Ferris, Dario A A Vignali
Author Information
Anthony R Cillo: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
Cornelius H L Kürten: Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Otorhinolaryngology, University Duisburg-Essen, 45147 Essen, Germany.
Tracy Tabib: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Zengbiao Qi: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Sayali Onkar: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
Ting Wang: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
Angen Liu: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Umamaheswar Duvvuri: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Seungwon Kim: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Ryan J Soose: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Steffi Oesterreich: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Women's Cancer Research Center. Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Wei Chen: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
Robert Lafyatis: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Tullia C Bruno: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address: tbruno@pitt.edu.
Robert L Ferris: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: ferrrl@upmc.edu.
Dario A A Vignali: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address: dvignali@pitt.edu.
Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environmental carcinogens or malignant transformation by human papillomavirus (HPV). Here, we assessed the transcriptional profiles of 131,224 single cells from peripheral and intra-tumoral immune populations from patients with HPV and HPV HNSCC and healthy donors. Immune cells within tumors of HPV and HPV HNSCC displayed a spectrum of transcriptional signatures, with helper CD4 T cells and B cells being relatively divergent and CD8+ T cells and CD4+ regulatory T cells being relatively similar. Transcriptional results were contextualized through multispectral immunofluorescence analyses and evaluating putative cell-cell communication based on spatial proximity. These analyses defined a gene expression signature associated with CD4 T follicular helper cells that is associated with longer progression-free survival in HNSCC patients. The datasets and analytical approaches herein provide a resource for the further study of the impact of immune cells on viral- and carcinogen-induced cancers.
