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Cytomegalovirus-induced oncomodulation in glioblastoma

ABSTRACT: Cytomegalovirus-induced oncomodulation drives immune escape in glioblastoma

PROVIDER: PRJEB85259 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR14216918_1.fastq.gz	Fastqsanger.gz
	ERR14216918_2.fastq.gz	Fastqsanger.gz
	ERR14216919_1.fastq.gz	Fastqsanger.gz
	ERR14216919_2.fastq.gz	Fastqsanger.gz
	ERR14216920_1.fastq.gz	Fastqsanger.gz

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Project description:Immune checkpoint blockers (ICBs) have failed in all Phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following anti-PD1 antibody treatment that disrupts the blood-tumor-barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.

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