Immune surveillance is critical to prevent tumorigenesis. Gliomas evade immune attack, but the underlying mechanisms remain poorly understood. We show that glioma cells can sustain growth independent of immune system constraint by reducing Notch signaling. Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Depletion of T cells simulates Notch inhibition and facilitates tumor initiation. Furthermore, Notch-depleted glioma cells acquire resistance to interferon-γ and TAMs re-educating therapy. Decreased interferon response and cytokine expression by human and mouse glioma cells correlate with low Notch activity. These effects are paralleled by upregulation of oncogenes and downregulation of quiescence genes. Hence, suppression of Notch signaling enables gliomas to evade immune surveillance and increases aggressiveness. Our findings provide insights into how brain tumor cells shape their microenvironment to evade immune niche control.

免疫监测对于预防肿瘤发生至关重要。胶质瘤逃避免疫攻击，但其潜在机制仍然知之甚少。我们表明，神经胶质瘤细胞可以通过减少 Notch 信号来维持独立于免疫系统限制的生长。神经胶质瘤小鼠模型中 Notch 活性的丧失会损害 MHC-I 和细胞因子的表达，并减少抗肿瘤免疫细胞群的募集，有利于免疫抑制性肿瘤相关小胶质细胞/巨噬细胞 (TAM)。T细胞的消耗模拟Notch抑制并促进肿瘤起始。此外，Notch 耗尽的神经胶质瘤细胞获得了对干扰素-γ 和 TAM 再教育疗法的抗性。人和小鼠神经胶质瘤细胞的干扰素反应和细胞因子表达降低与 Notch 活性低相关。这些效应与癌基因的上调和静止基因的下调平行。因此，抑制 Notch 信号使神经胶质瘤能够逃避免疫监视并增加侵袭性。我们的研究结果提供了有关脑肿瘤细胞如何塑造其微环境以逃避免疫生态位控制的见解。