Humanized PD-1 Knock-in Mice Reveal Nivolumab's Inhibitory Effects on Glioblastoma Tumor Progression In Vivo

Abstract

Background/aim: Immunotherapy has been considered a promising approach for brain tumor treatment since the discovery of the brain lymphatic system. Glioblastoma (GBM), the most aggressive type of brain tumor, is associated with poor prognosis and a lack of effective treatment options.

Materials and methods: To test the efficacy of human anti-PD-1, we used a humanized PD-1 knock-in mouse to establish an orthotopic GBM-bearing model.

Results: Nivolumab, a human anti-PD-1, effectively inhibited tumor growth, increased the survival rate of mice, enhanced the accumulation and function of cytotoxic T cells, reduced the accumulation and function of immunosuppressive cells and their related factors, and did not induce tissue damage or biochemical changes. The treatment also induced the accumulation and activation of CD8⁺ cytotoxic T cells, while reducing the accumulation and activation of myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages in the immune microenvironment.

Conclusion: Nivolumab has the potential to be a treatment for GBM.

Keywords: Glioblastoma; cytotoxic T cells; humanized PD-1 knock-in mouse; immune microenvironment; nivolumab.