| First Author | Chen D | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 9 | Pages | 2086-2104.e8 |
| PubMed ID | 37572655 | Mgi Jnum | J:341108 |
| Mgi Id | MGI:7528594 | Doi | 10.1016/j.immuni.2023.07.015 |
| Citation | Chen D, et al. (2023) CTLA-4 blockade induces a microglia-Th1 cell partnership that stimulates microglia phagocytosis and anti-tumor function in glioblastoma. Immunity 56(9):2086-2104.e8 |
| abstractText | The limited efficacy of immunotherapies against glioblastoma underscores the urgency of better understanding immunity in the central nervous system. We found that treatment with alphaCTLA-4, but not alphaPD-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. alphaCTLA-4 treatment increased frequencies of intratumoral IFNgamma-producing CD4(+) T cells, and IFNgamma blockade negated the therapeutic impact of alphaCTLA-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 IFNgamma-dependent microglia activation and phagocytosis via the AXL/MER tyrosine kinase receptors, which were necessary for tumor suppression. Thus, alphaCTLA-4 blockade in mesenchymal-like glioblastoma promotes a CD4(+) T cell-microglia circuit wherein IFNgamma triggers microglia activation and phagocytosis and microglia in turn act as antigen-presenting cells fueling the CD4(+) T cell response. |
