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.

免疫抑制性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的患者的反应率，例如程序性死亡 1 （PD-1） 和程序性死亡配体 1 （PD-L1）。在这里，我们证明了金属离子螯合 l-苯丙氨酸纳米结构与短期饥饿 （STS） 协同作用，以重塑乳腺癌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 炎性小体和钙介导的核因子-κB 通路激活它们。STS 通过氨基酸转运蛋白促进细胞对纳米结构的摄取，并在树突状细胞成熟和肿瘤特异性细胞毒性 T 淋巴细胞反应中起关键作用。本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。