An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating l-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating l-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy.

免疫抑制肿瘤微环境强烈影响接受基于免疫检查点阻断的癌症免疫疗法（例如程序性死亡-1 (PD-1) 和程序性死亡配体 1 (PD-L1)）的患者的反应率。在这里，我们证明金属离子螯合的L-苯丙氨酸纳米结构与短期饥饿（STS）协同作用，重塑乳腺和结直肠肿瘤的免疫抑制微环境。这些纳米结构调节树突状细胞的电生理行为，并通过 NLRP3 炎性体和钙介导的核因子-κB 途径激活它们。 STS 通过氨基酸转运蛋白促进纳米结构的细胞摄取，并在树突状细胞成熟和肿瘤特异性细胞毒性 T 淋巴细胞反应中发挥关键作用。这项研究证明了金属离子螯合L-苯丙氨酸纳米结构在激活免疫反应中的潜在作用以及 STS 治疗在改善纳米材料介导的癌症免疫治疗中的作用。