Oncolytic virotherapy improves immunotherapies targeting cancer stemness in glioblastoma

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 9; p. 130662
• Main Authors: Keshavarz, Mohsen, Dianat-Moghadam, Hassan, Ghorbanhosseini, Seyedeh Sara, Sarshari, Behrang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Animals; Brain Neoplasms - immunology; Brain Neoplasms - pathology; Brain Neoplasms - therapy; CAR-T cell; cell death; central nervous system; Drug resistance; Glioblastoma; Glioblastoma - immunology; Glioblastoma - pathology; Glioblastoma - therapy; Glioma stem cells; Humans; Immunogenic cell death; immunogenicity; immunotherapy; Immunotherapy - methods; landscapes; neoplasm progression; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - pathology; Oncolytic Virotherapy - methods; Oncolytic viruses; Oncolytic Viruses - immunology; Tumor Microenvironment - immunology; Oncolytic viruses; Glioma stem cells; Drug resistance; CAR-T cell; Immunogenic cell death; Glioblastoma
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130662

Despite advances in cancer therapies, glioblastoma (GBM) remains the most resistant and recurrent tumor in the central nervous system. GBM tumor microenvironment (TME) is a highly dynamic landscape consistent with alteration in tumor infiltration cells, playing a critical role in tumor progression and invasion. In addition, glioma stem cells (GSCs) with self-renewal capability promote tumor recurrence and induce therapy resistance, which all have complicated eradication of GBM with existing therapies. Oncolytic virotherapy is a promising field of therapy that can kill tumor cells in a targeted manner. Manipulated oncolytic viruses (OVs) improve cancer immunotherapy by directly lysis tumor cells, infiltrating antitumor cells, inducing immunogenic cell death, and sensitizing immune-resistant TME to an immune-responsive hot state. Importantly, OVs can target stemness–driven GBM progression. In this review, we will discuss how OVs as a therapeutic option target GBM, especially the GSC subpopulation, and induce immunogenicity to remodel the TME, which subsequently enhances immunotherapies' efficiency. [Display omitted] •OVs have potency in selecting and killing tumor cells, recruiting effector immune cells to tumor sites.•OVs mediating targeting of the GSCs niche can reprogram TME of GBM.•Targeting cancer stemness through engineered OVs improves antitumoral responses.•The combination of OVs and immunotherapies significantly improved outcomes in the GBM model.