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

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. Gl261-infiltrating CD11b+ cells (CD45highCD11b+) were purified for anti-CTLA-4 + anti-PD-1 responder and non-responder mice by fluorescence-activated cell sorting and gene expression analysis was performed by NanoString analysis.