Researchers at the University of California San Diego School of Medicine and at the UC San Diego Moores Cancer Center have identified a strong association between telomerase reverse transcriptase (TERT), an antigen abundantly produced in roughly 85% of tumor cells, and elevated levels of white blood cells that produce antibodies within tumors. This correlation is particularly strong in head and neck squamous cell carcinoma (HNSCC), one of the most common head and neck cancers.
In the study, published in PNAS Nexus (2023;2:pgad046), researchers analyzed tumor RNA sequencing data from the Cancer Genome Atlas for 4,535 patients representing 11 solid cancer types to investigate potential interactions between TERT expression and B and T cells that have infiltrated the tumor microenvironment. They found a positive correlation between TERT expression and B and T cells in four cancer types, with the strongest association in HNSCC. Researchers also found that patients in which this association was found are linked to more favorable clinical outcomes—a Bhigh/TERThigh signature was associated with improved progression-free survival (P = 0.0048), an effect that was independent of human papillomavirus (HPV) status and wasn’t shared in comparable analysis by other conserved tumor antigens.
These results have implications for the development of new forms of immunotherapy in patients with HPV-negative HNSCC, said co-senior study author Maurizio Zanetti, MD, a professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at Moores Cancer Center in Calif., in a press release. “The current emphasis is on neoantigens (proteins that form on cancer cells when certain mutations occur in tumor DNA) and immune checkpoint inhibitors (drugs such as monoclonal antibodies) that target and block actions that help shield cancer cells from attack by T cells. But these therapies are only partially effective and in some types of cancer only. Our findings provide evidence that high TERT expression is a key signal that generates high levels of B and T cells intra-tumor, suggesting a new way to develop intra-tumor immunotherapies to reinforce anti-tumor immunity already in place.”