The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (T_H17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T_H17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T_H17-cell-mediated anti-tumour responses. The nanoparticles activate the pattern-recognition receptor Dectin-2 and Toll-like receptor 4 in dendritic cells, and promote the differentiation of CD4⁺ T cells into the T_H17 phenotype. In mice, intra-tumoural administration of the nanoparticles decreased the fraction of regulatory T cells in the tumour while markedly increasing the fractions of T_H17 cells (and the levels of T_H17-cell-associated cytokines), CD8⁺ T cells, natural killer cells and M1-like macrophages. The anti-tumoural activity of the effector cells was amplified by an agonistic antibody against the co-stimulatory receptor OX40 in multiple mouse models. Nanomaterials that induce T_H17-cell-mediated immune responses may have therapeutic potential.

免疫抑制性肿瘤微环境阻碍了癌症免疫疗法的有效性，而效应 T 细胞和自然杀伤细胞的渗透性较差。在感染和自身免疫性疾病中，效应免疫细胞的招募和激活是由促炎辅助性 T 17 (T _H 17) 细胞协调的。在这里，我们展示了展示甘露聚糖（一种激活微生物细胞壁中 T _H 17 细胞的多糖）的模拟病原体中空纳米粒子，限制了调节性 T 细胞的比例并诱导 T _H 17 细胞介导的抗肿瘤反应。纳米粒子激活树突状细胞中的模式识别受体Dectin-2和Toll样受体4，并促进CD4 ⁺ T细胞分化为T _H 17表型。在小鼠中，肿瘤内施用纳米颗粒降低了肿瘤中调节性 T 细胞的比例，同时显着增加了 T _H 17 细胞的比例（以及 T _H 17 细胞相关细胞因子的水平）、CD8 ⁺ T 细胞、自然杀伤细胞和 M1 样巨噬细胞。在多种小鼠模型中，针对共刺激受体 OX40 的激动性抗体增强了效应细胞的抗肿瘤活性。诱导 T _H 17 细胞介导的免疫反应的纳米材料可能具有治疗潜力。