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Landscape of immune checkpoint blockade-induced immune alterations in the microenvironment of primary and metastatic brain tumors

ABSTRACT: Brain tumors reside in an immune privileged microenvironment where inflammatory processes are heavily regulated. Nevertheless, our recent study showed a significant immune infiltration in recurrent glioblastoma (rGBM) treated with neoadjuvant PD-1 checkpoint blockade therapy. Compared to GBM, the intracranial immunotherapy response of brain metastases (BrM) has been much less studied. Therefore we studied the effect of pre-surgical immune checkpoint blockade (ICB) on the immune compartments of BrM, using multiplex immunofluorescence, mass cytometry and single-cell RNA sequencing. ICB induced much higher T cell infiltration in BrM compared to rGBM. It also caused the loss of a unique perivascular macrophage subset (CD206+LYVE1+), the absence of which associated with the enhanced T cell infiltration in BrM. These T cells produced high levels of IFN-γ that elicited and interferon response transcriptional program in the tumor-associated myeloid cells. T cell-myeloid interactions were also strengthened by ICB in BrM and might have led to the terminal exhaustion of the infiltrating T cells. Our results emphasize the importance of adopting novel immune-boosting approaches to rejuvenate the systemic T cell pool so as to improve tumor control of brain metastases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193745 | GEO | 2023/07/06

REPOSITORIES: GEO

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