Head and neck squamous cell carcinoma (HNSCC), particularly cases that are not caused by human papillomavirus (HPV), is highly resistant to standard treatments and often results in worse outcomes than HPV-associated disease. While the use of immunotherapy shows promise in these types of head and neck cancers by strengthening the body’s immune response, doctors still face significant challenges when trying to control the disease long-term.
MCW cancer researchers may have uncovered a way to make immunotherapy more effective for patients with HNSCC. In a new study, they discovered that tumor-infiltrating lymphocytes (TILs)—special T cells capable of recognizing and killing cancer cells—could be taken out of patients’ tumors and made stronger to fight their disease. They then examined TILs one by one and identified which specific immune cells were responsible for the cancer-killing. These findings, recently published in Translational Oncology, represent a big step forward in the understanding of HNSCC and may lead to life-saving treatments for patients in Wisconsin and beyond.
“Despite the tumor’s attempts to evade the immune system, TILs showed signs of retaining their ability to fight cancer. Even in cases where tumors were resistant to radiation or had depleted T cell populations, the TILs displayed promising functionality when activated,” said Joseph Zenga, MD, Assistant Professor of Otolaryngology and first author of the study. “Our use of optofluidic technology from the Cancer Center’s Cell Therapy Shared Resource (CTSR) is particularly noteworthy, as it enabled the identification and visualization of individual tumor-killing TILs in real-time.”
“This research lays the groundwork for personalized treatments tailored to each patient’s specific tumor, which could positively impact survival outcomes for people with HNSCC. Additionally, the methods used in this study may be applicable to many solid tumors, beyond just head and neck cancers,” said Dr. Zenga.
The study team examined TILs from tumors of 31 patients with HPV-negative HNSCC, taken during surgery. The CTSR’s cutting-edge Bruker Cellular Analysis Lightning platform allowed them to place individual tumor cells and individual TILs in small wells so they could watch them interact one-on-one, providing valuable insights into the dynamics of T cell-mediated tumor killing. “If we can identify tumor-killing TILs on a single-cell level, we can figure out which receptors they use to recognize and kill cancer. This would allow us to engineer T cells with tumor-killing receptors which we could develop to achieve personalized T cell therapies for our patients,” said Dr. Zenga.
In 2024, head and neck cancers will account for more than 70,000 new diagnoses in the United States. Scientists from MCW’s Head and Neck group remain dedicated to research that will enhance the quality of life for patients and families experiencing the disease. Dr. Zenga said the team’s next steps are to sequence the receptors from individual tumor-killing T cells; and to develop a gene signature from single-cell sequencing analyses of tumor biopsies, which can predict tumor-killing T cells for each patient.
“Science is a team sport! A big thank you to Drs. Heather Himburg, Musaddiq Awan, and Stuart Wong, and to lab team members Anne Frei, Jaime Foeckler, and Josh House for their contributions to this study. I also want to extend my appreciation to Drs. Tyce Kearl, Peiman Hematti, and Fanghong Chen of the CTSR for their support and collaboration,” said Dr. Zenga.
Read the full study in Translational Oncology.