Neoadjuvant anti-PD-1 immunotherapy for recurrent glioblastoma

Dana Mitchell, Mahua Dey


In a healthy host, the programmed cell death (PD) pathway serves to regulate T cell activity in order to prevent damage secondary to chronic inflammation and the development of autoimmunity. This pathway is often exploited by human cancers to suppress infiltrating cytotoxic T lymphocytes (CTLs) and evade the anti-tumor immune response (1). Cancers, including glioblastoma (GBM), upregulate the expression of PD-L1, which upon binding to PD-1 expressed on the surface of T cells, results in the attenuation of T cell activity (2). The resulting attenuation of the anti-tumor T cell response is achieved through the suppression of T cell proliferation and cytokine release as well as the induction of T cell anergy, promotion of T cell apoptosis and expansion of the regulatory T cell (Tregs) population (1,2).