| First Author | Liu H | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 4 | Pages | 693-710.e8 |
| PubMed ID | 36963400 | Mgi Jnum | J:359177 |
| Mgi Id | MGI:7463778 | Doi | 10.1016/j.ccell.2023.03.004 |
| Citation | Liu H, et al. (2023) Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma. Cancer Cell 41(4):693-710.e8 |
| abstractText | Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8(+) T subsets, as well as cytotoxic CD4(+) T subsets. Notably, a distinct subpopulation of CD4(+) T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4(+) T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma. |
