富含乳酸的肿瘤微环境（TME）培育免疫抑制环境，阻碍肿瘤相关巨噬细胞（TAM）的功能。然而，解决乳酸积累造成的免疫抑制作用仍然是一个巨大的挑战。在此，我们构建了一个双酶驱动级联反应平台（ILH），具有免疫抑制 TME 调节，用于光声（PA）成像引导的催化治疗和免疫激活。 ILH 由铱 (Ir) 金属纳米酶、乳酸氧化酶 (LOx) 和透明质酸 (HA) 组成。 Ir纳米酶与LOx的组合不仅可以有效消耗乳酸，通过促进TAM从M2表型极化到M1表型，从而将免疫抑制性TME逆转为免疫反应性TME，从而增强抗肿瘤防御能力，而且可以缓解肿瘤缺氧并诱导强效TME。氧化应激，从而引发免疫原性细胞死亡（ICD）并激活抗肿瘤免疫。此外，Ir纳米酶的光热性能可以增强级联催化能力并赋予ILH PA响应。基于内源性分子PA信号的变化，利用三维多光谱PA成像来追踪体内级联催化治疗的过程。这项工作为双酶驱动的级联催化治疗和通过调节免疫抑制 TME 来激活免疫提供了一个纳米平台。

Lactate-enriched tumor microenvironment (TME) fosters an immunosuppressive milieu to hamper the functionality of tumor-associated macrophages (TAMs). However, tackling the immunosuppressive effects wrought by lactate accumulation is still a big challenge. Herein, we construct a dual enzyme-driven cascade reaction platform (ILH) with immunosuppressive TME modulation for photoacoustic (PA) imaging-guided catalytic therapy and immune activation. The ILH is composed of iridium (Ir) metallene nanozyme, lactate oxidase (LOx), and hyaluronic acid (HA). The combination of Ir nanozyme and LOx can not only efficiently consume lactate to reverse the immunosuppressive TME into an immunoreactive one by promoting the polarization of TAMs from the M2 to M1 phenotype, thus enhancing antitumor defense, but also alleviate tumor hypoxia as well as induce strong oxidative stress, thus triggering immunogenic cell death (ICD) and activating antitumor immunity. Furthermore, the photothermal performance of Ir nanozyme can strengthen the cascade catalytic ability and endow ILH with a PA response. Based on the changes in PA signals from endogenous molecules, three-dimensional multispectral PA imaging was utilized to track the process of cascade catalytic therapy in vivo. This work provides a nanoplatform for dual enzyme-driven cascade catalytic therapy and immune activation by regulating the immunosuppressive TME.