Glioblastoma cellular MAP4K1 facilitates cancer cell proliferation and disrupts T effector cell infiltration

Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1) has been implicated as a cancer immunotherapy target. However, whether cancer-cell-intrinsic MAP4K1 contributes to tumor progression and immunological microenvironment remain elusive. We found that MAP4K1 proteins were highly expressed in glioblastoma multiforme (GBM) cells of human glioma specimens. High levels of MAP4K1 mRNA correlated with the poor prognosis of patients with gliomas. MAP4K1 silencing inhibited the proliferation GBM cells. Transcriptome analysis of GBM tissues and GBM cells showed that MAP4K1 was positively correlated with cytokine-cytokine receptor interaction including interleukin-18 receptor (IL-18R) and IL-6R pathway.Additionally, GBM-cell-derived MAP4K1 reduced CD8+ T cell infiltration in mouse and human glioma models and impaired CD8+ T cell migration. Our findings provide a novel insight into the pathological significance of GBM-cell-intrinsic MAP4K1 in driving tumor growth and resistance to antitumor immunity by remodeling cytokine-chemokine network.