近红外（NIR）激光诱导的光免疫疗法因其固有的非侵入性和时空精确性而引起了人们的极大兴趣，而乳酸（LA）积累引起的免疫逃避严重限制了其临床结果。尽管一些代谢干预措施已致力于改善免疫抑制，但细胞内残留的 LA 仍然是嗜酸细胞增殖的潜在能量来源。在此，我们构建了一种基于蛋黄壳CoP/NiCoP（CNCP）异质结构的免疫调节纳米佐剂，负载有单羧酸转运蛋白4（MCT4）抑制剂氟伐他汀钠（Flu），可同时缓解免疫抑制并引发强大的抗肿瘤免疫力。在近红外辐射下，CNCP异质结表现出优异的光热性能以及光催化产生活性氧（ROS）和氢气的性能。然后，持续的热量促进 Flu 释放，抑制肿瘤细胞的 LA 渗出，而累积的 LA 可以作为空穴清除剂被耗尽，以提高光催化效率。随后，强化光催化疗法（PCT）不仅可以启动系统免疫反应，还可以引起严重的线粒体功能障碍，扰乱热休克蛋白（HSP）合成的能量供应，从而实现温和的光热疗法（PTT）。因此，LA代谢重塑赋予了具有最佳安全性的密集级联治疗，可有效抑制肿瘤增殖和转移，这为代谢调节免疫治疗的发展提供了新的范例。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic non-invasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, we construct an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 (MCT4) inhibitor fluvastatin sodium (Flu) to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species (ROS) and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy (PCT) can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein (HSP) synthesis, in turn realizing mild photothermal therapy (PTT). Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.