Measles Virus-Based Treatments Trigger a Pro-inflammatory Cascade and a Distinctive Immunopeptidome in Glioblastoma

Area of Science:

• Neuro-oncology
• Virology
• Immunology

Background:

• Glioblastoma is an aggressive brain tumor with a poor prognosis.
• Oncolytic measles virus (MeV) shows potential as a glioma treatment, with demonstrated clinical safety and early signs of efficacy.

Purpose of the Study:

• To investigate the synergistic effects of combining MeV virotherapy with conventional chemotherapy and radiotherapy (CT-VT-RT) for glioblastoma.
• To delineate the molecular and immunological changes induced by this combination therapy.

Main Methods:

• Cytotoxic survival assays were performed on long-term glioma cell lines and primary glioblastoma cultures.
• Chou-Talalay analysis determined the optimal synergistic treatment sequence (CT-VT-RT).
• RNA sequencing and immunopeptidome analyses (HLA ligandome) were used to profile molecular and immunological responses.

Main Results:

• The CT-VT-RT sequence demonstrated synergistic anti-glioma activity.
• The combination therapy induced a type 1 interferon response, activating Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling.
• Increased antigen presentation and immunostimulatory chemokines were observed, creating a pro-inflammatory tumor phenotype and inducing apoptotic cascades.

Conclusions:

• The CT-VT-RT combination therapy exhibits a synergistic anti-glioma effect and elicits a pro-inflammatory immune response.
• This treatment induces a distinct molecular and immunological signature, including the presentation of novel viral and tumor-associated peptides.
• These findings support the development of tailored treatment strategies combining virotherapy and immunotherapy for glioblastoma.