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New Study Provides Extensive Profile of Head and Neck Squamous Cell Carcinoma Tumor Microenvironment, Cellular Constituents, and Cell-Cell Interactions

January 3, 2022

In a new paper published in December 2021 in the journal Nature Communications, a multidisciplinary team of researchers from UPMC and the University of Pittsburgh provides the most comprehensive analysis to date on the tumor microenvironment, cellular composition, and transcriptomic cell-cell interactions in head and neck squamous cell carcinoma (HNSCC). This research is designed to aid in developing more effective immunotherapy approaches to treating HNSCC and better target treatment modalities for individual patients based upon their unique cancer tumor and cellular biological profile.

Robert L. Ferris, MD, PhD, director of UPMC Hillman Cancer Center and professor of Oncology, Otolaryngology, and Immunology at the University of Pittsburgh School of Medicine, was the study's senior author. 

The study conducted by the research team employed single-cell RNA sequencing technology to extensively analyze and profile cells in the cancer tumor microenvironment in patients with either human papillomavirus positive (HPV+) or negative (HPV-) HNSCC. The study compared patients with HPV+ and HPV- cancer types, and it compared the various types of cancerous and noncancerous cells present to comprehensively profile the populations.

Through single-cell RNA sequencing, the investigators examined and profiled 134,606 cells, making the results from this study the most comprehensive data set of cells and their transcriptomic activities in the tumor microenvironment for HNSCC created to date. 

The study generated several new and important insights about the composition of HNSCC cells and their interactions within the tumor microenvironment.

Study Highlights and Clinical Significance

One key finding from the study identified cell type-specific transcriptomic signatures specific to the HPV status of the patient’s cancer and whether the tumors were in a proinflammatory state from T cell infiltration versus non-inflamed tumors. 

The study also found that a specific class of fibroblasts — fibroblasts with elastic differentiation — were associated with poor prognosis but only in HPV-positive cancers. HPV+ HNSCC with both lower levels of this type of fibroblast, and lower levels of cancer-associated fibroblasts showed the highest levels overall survival.

Furthermore, the analysis uncovered data indicating that tumor-associated macrophages, more so than any other cell types, contribute to the presence of immune checkpoint ligands, such as PD-L1, detected within the tumor microenvironment.

“This and other findings from our study emphasize and support the compelling need to classify HPV+ and HPV- HNSCC as two discrete disease states that will require differentiated and highly-targeted approaches to treatment in order to realize optimal outcomes and improve overall survival for patients," says Dr. Ferris.

The cellular and transcriptomic findings from this study ultimately could help to identify novel biomarkers useful for projecting cancer prognosis, amenability to various treatment modalities or agents, as well as develop new therapeutic targets for translational investigations designed to develop more personalized approaches to treatment based on disease type, tumor composition, and cell-specific interactions. 

The data created from this study serves as an essential new resource for HNSCC investigators working to better understand disease processes and develop new therapeutics. The UPMC and University of Pittsburgh research team will continue to explore the results from this study in the pursuit of further discoveries about HNSCC.

Learn more about the study using the reference below. 


Kürten CHL, Kulkarni A, Cillo AR, Santos PM, Roble AK, Onkar S, Reeder C, Lang S, Chen X, Duvvuri U, Kim S, Liu A, Tabib T, Lafyatis, Feng J, Gao S-J, Bruno TC, Vignali DAA, Lu X, Bao R, Lazar V, Ferris RL. Investigating Immune and Non-Immune Cell Interactions in Head and Neck Tumors by Single-cell RNA Sequencing. Nat Commun. 2021 December 17. Epub ahead of print.