Cellular image showing T-cells in red and yellow.
Researchers at Winship Cancer Institute of Emory University played a leading role in two new studies which could change the way oncologists treat oral cavity squamous cell carcinoma (OCSCC), the most common form of head and neck cancer.
The findings, published in Cell Reports Medicine, found that pre-surgery immunotherapy is safe and effective in treating some patients with OCSCC. The studies resulted from a collaboration between Winship, MUSC Hollings Cancer Center and UCLA Jonsson Comprehensive Cancer Center.
OCSCC is a highly invasive and resistant form of cancer which kills more than 10,000 Americans a year. Many patients must undergo disfiguring surgery. Even after surgery, only 60 percent of patients were still alive after five years. Smoking is a major risk factor for developing OCSCC.
Researchers tested the efficacy of treating patients prior to surgery with the immune checkpoint inhibitor anti-PD-1, which has revolutionized the way patients with advanced other malignancies are treated. In the process, they identified potential molecular biomarkers in the blood and tumors of patients that show how likely they would be to respond to immunotherapy.
Chrystal Paulos, PhD, an associate professor in the Department of Surgery and Department of Microbiology and Immunology at Emory School of Medicine and a Winship researcher, said that a multi-disciplinary approach with experts in three distinct disciplines – clinical medicine, immunology, and high-profile sequencing – helped uncover the important findings in this work.
"Our work collaborates with other investigators and shows that neoadjuvant immunotherapy can augment responses in patients." says Paulos co-senior author of both the studies. "We found that the ratio of effector T helper 17 cells to regulatory T cells in the tumor might predict if a patient is responsive or not to this new treatment."
"This work can be exploited in the future to design new clinical trials aiming to increase the number of patients responsive to the therapy," Paulos adds.
Hannah Knochelmann, PhD, is a MSTP student at the Medical University of South Carolina and visiting student at Emory University.
"It was exciting to be part of a team built across three major institutions with a shared goal to improve outcomes to immunotherapy in head and neck cancer patients," Knochelmann says. "Understanding why some patients respond well to therapy and others do not is a critical part of designing therapies that help more cancer patients in the long run, which was a key motivating factor for us."
The other two co-senior authors of the works are Hollings researcher David Neskey, MD, who is an assistant professor of Otolaryngology--Head & Neck Surgery at the Medical University of South Carolina, and Roger Lo, MD, PhD, professor of medicine at the David Geffen School of Medicine at UCLA and member of the UCLA Jonsson Comprehensive Cancer Center.
The studies were based on a phase two clinical trial of nivolumab, an anti-PD-1 antibody, that was given to 12 patients in South Carolina with stage 2 to stage 4A OCSCC prior to surgery. Patients were evaluated by how their tumor responded to treatment. Patients who showed a response to treatment, meaning their tumor shrunk in size, were given the antibody every two weeks for a total of 4 doses, and then proceeded to surgery. Those patients who did not respond to the first three doses went directly to surgery.
Of the patients who took part in the study, four showed a positive response to treatment, four had stable disease, and four had a disease that progressed. The results demonstrate feasibility and safety for incorporation of nivolumab in a neoadjuvant setting for OCSCC patients.
View publications:
- H. Knochelmann et al, Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma, Cell Reports Medicine (2021)
- S. Liu et al, Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma, Cell Reports Medicine (2021)
