CTLA-4 blockade induces a microglia-Th1 cell partnership that stimulates microglia phagocytosis and anti-tumor function in glioblastoma.

ABSTRACT: The limited efficacy of immunotherapies against glioblastoma underscores the urgency of better understanding immunity in the central nervous system. We found that treatment with αCTLA-4, but not αPD-1, prolonged survival in a mouse model of mesenchymal-like glioblastoma. This effect was lost upon the depletion of CD4⁺ T cells but not CD8⁺ T cells. αCTLA-4 treatment increased frequencies of intratumoral IFNγ-producing CD4⁺ T cells, and IFNγ blockade negated the therapeutic impact of αCTLA-4. The anti-tumor activity of CD4⁺ T cells did not require tumor-intrinsic MHC-II expression but rather required conventional dendritic cells as well as MHC-II expression on microglia. CD4⁺ T cells interacted directly with microglia, promoting IFNγ-dep

SUBMITTER: Chen D 

PROVIDER: S-EPMC11800830 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature