肿瘤相关巨噬细胞（TAMs）是肿瘤微环境（TME）中重要的免疫细胞。TAMs的极性可塑性使其成为改善肿瘤免疫抑制微环境的重要靶点。我们之前的研究发现，层状双金属氢氧化物（LDHs）能够有效促进TAMs从抗炎性M2型转化为促炎性M1型的极性。然而，LDHs的作用机制尚未被探索。本研究揭示了由不同阳离子组成的LDHs呈现出不同的调节TAMs极性的能力。与Mg-Fe LDH相比，Mg-Al LDH更能有效促进TAMs从M2向M1的重新极性化，并抑制髓样衍生抑制性细胞（MDSCs）的形成。此外，Mg-Al LDH更有效地抑制肿瘤的生长，并促进激活的免疫细胞更好地渗入TME。有趣的是，Mg-Al LDH影响了TAMs的自噬，这与TAMs的促炎能力负相关。因此，LDHs通过抑制TAMs的自噬来发挥其极化能力，而该机制可能与LDHs的离子组成有关。本研究为优化基于LDHs的免疫佐剂的性能奠定了基础，这显示了肿瘤免疫治疗的出色应用前景。版权所有，未经许可，严禁转载。

Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). The polar plasticity of TAMs makes them important targets for improving the immunosuppressive microenvironment of tumors. Our previous study revealed that layered double hydroxides (LDHs) can effectively promote the polarization of TAMs from the anti-inflammatory M2 type to the pro-inflammatory M1 type. However, their mechanisms of action remain unexplored. This study revealed that LDHs composed of different cations exhibit distinct abilities to regulate the polarity of TAMs. Compared to Mg-Fe LDH, Mg-Al LDH has a stronger ability to promote the repolarization of TAMs from M2 to M1 and inhibit the formation of myeloid-derived suppressor cells (MDSCs). In addition, Mg-Al LDH restrains the growth of tumors in vivo and promotes the infiltration of activated immune cells into the TME more effectively. Interestingly, Mg-Al LDH influenced the autophagy of TAMs; this negatively correlated with the pro-inflammatory ability of TAMs. Therefore, LDHs exert their polarization ability by inhibiting the autophagy of TAMs, and this mechanism might be related to the ionic composition of LDHs. This study lays the foundation for optimizing the performance of LDH-based immune adjuvants, which display excellent application prospects for tumor immunotherapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.