CD103⁺ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8⁺ T cell activation in glioblastoma.

ABSTRACT: Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due to their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in T cell content. Orthogonally, spatial imaging mass cytometry shows T cell enrichment in human recurrent tumors compared with matched primary glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak of T cell infiltration post-radiotherapy results in a modest survival benefit compared with concurrent α-PD-1 administration. Following α-PD-1 therapy, CD103⁺ regulatory T cells (Tregs) with upregulated lipid metabolism accumulate in the tumor microenvironment, and

SUBMITTER: van Hooren L 

PROVIDER: S-EPMC10212765 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature