Role of intratumoral CD11b+ cells in immune checkpoint resistance in GBM

ABSTRACT: Glioblastomas show low response rates to immune checkpoint blockade with few hypermutated glioblastomas showing responses. Moreover, a growing body of evidence suggests that macrophages in the glioblastoma microenvironment impair anti-tumor immunity and immunotherapy approaches. Here, we investigate macrophage-mediated mechanisms of response and resistance to combinatory immune checkpoint blockade targeting PD-1 and CTLA-4 in the murine syngeneic Gl261 glioblastoma model. Nanostring analysis from CD45highCD11b+ cells isolated from ICB responder and non-responder Gl261 tumors was performed. Here, we provide evidence for a differential expression of pro- and anti-inflammatory genes in CD45highCD11b+ cells from ICB responder and non-responder tumors pointing towards a suppressive phenotype of ICB non-responder CD45highCD11b+ cells. Targeting these suppressive CD45highCD11b+ cells in the glioblastoma microvenvironment might thus potentiate ICB efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE129877 | GEO | 2020/02/03

REPOSITORIES: GEO