A Nitrated T-Cell Epitope Enhances the Antitumor Immune Response of a TOPK-Targeted Vaccine in Glioblastoma and Its Potential for Remodeling the Tumor Microenvironment

Background: Glioblastoma (GBM) remains the most lethal primary brain tumor in adults, largely due to recurrence after surgery. Cancer vaccines, which can activate a patient’s adaptive immune system against specific tumor antigens, are a promising strategy for improving outcomes in patients with GBM. Methods: We examined the function of T-lymphokine-activated killer cell-originated protein kinase (TOPK), a candidate tumor-associated antigen, in GBM. We then constructed TOPK-NitraTh, a vaccine coupled to a nitrated T-cell epitope (NitraTh) and targeting TOPK. Its efficacy was evaluated in the GL261 orthotopic GBM model, and single-cell RNA sequencing was used to explore the underlying immune mechanisms. Results: TOPK functioned as a tumor-promoting factor in GBM. Vaccination with TOPK-NitraTh elicited TOPK-specific adaptive immune responses and inhibited GBM progression in the GL261 orthotopic model. Exploratory single-cell RNA sequencing analysis led us to hypothesize that the NitraTh-based vaccine may reprogram macrophages potentially via the NF-κB signaling pathway, potentially contributing to the reversal of the immunosuppressive tumor microenvironment. Conclusions: Given its ability to remodel the tumor microenvironment, the NitraTh-based vaccine represents a promising preclinical strategy for GBM treatment.