B-cells Drive Response to PD-1 Blockade in Glioblastoma Upon Neutralization of TGFβ-mediated Immunosuppression.

ABSTRACT: Immunotherapy has revolutionized cancer treatment but has yet to be translated into brain tumors. Studies in other solid tumors suggest a central role of B-cell immunity in driving immune-checkpoint-blockade efficacy. Using single-cell and single-nuclei transcriptomics of human glioblastoma and melanoma brain metastasis, we found that tumor-associated B-cells have high expression of checkpoint molecules, known to block B-cell-receptor downstream effector function such as plasmablast differentiation and antigen-presentation. We also identified TGFβ-1/TGFβ receptor-2 interaction as a crucial modulator of B-cell suppression. Treatment of glioblastoma patients with pembrolizumab induced expression of B-cell checkpoint molecules and TGFβ-receptor-2. Abrogation of TGFβ using different conditiona

SUBMITTER: Hou D 

PROVIDER: S-EPMC9882679 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature