Understanding the Direct Impact of Agonistic Immunotherapies on Glioblastoma Cells

Department

University of Virginia, 1827 University Avenue, Charlottesville, VA 22903.

Document Type

Poster

Publication Date

4-17-2026

Abstract

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant brain tumors, characterized by high invasiveness and limited effective therapies. The CT2A murine glioma model serves as a translational platform for studying immunotherapeutic strategies due to its similarities to human GBM. This project investigated whether agonistic treatments directly affect GBM tumor cells and whether such interactions could enhance therapeutic outcomes. Previous studies showed that combining therapeutic αCD40, αPD1, and poly(I:C) significantly improves survival in mice through a T cell–dependent mechanism. We therefore examined whether tumor cells themselves could directly respond to these agonistic agents, potentially increasing their susceptibility to T cell–mediated immune attack. CT2A ZsGreen-transduced GBM cells were cultured and treated with αCD40, poly(I:C), both agents, or control IgG2a. Flow cytometry showed that poly(I:C) alone increased MHC I expression, while MHC II levels remained unchanged. We then tested concentration-dependent effects of poly(I:C) (100, 225, and 350 µg/mL) on MHC I, MHC II, PD-L1, and CD40 expression. MHC I and MHC II showed similar patterns, PD-L1 expression peaked at the highest dose, and CD40 peaked at the mid dose. However, these effects were modest, with fewer than 5% of live cells showing increased expression and only at supraphysiological poly(I:C) levels. Because effective anti-tumor responses often involve interferon-gamma (IFN-γ) production, we also examined whether overnight stimulation altered expression of PD-L1, CD40, MHC I, or MHC II. No clear differences were observed between treated and untreated samples. Overall, these findings suggest the therapies primarily act through immune system activation rather than direct tumor cell effects, helping explain the improved survival observed in prior studies.

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