锰 (Mn) 在体内的各种生物过程中发挥着至关重要的作用。研究主要集中在它们增强免疫细胞功能和激活抗肿瘤能力的能力，特别是树突状细胞 (DC)、巨噬细胞和 T 细胞。肿瘤相关巨噬细胞（TAM）通常是肿瘤微环境（TME）中最丰富的免疫细胞群。因此，研究 Mn2 调节 TAM 参与抗肿瘤免疫的机制是有价值的，因为它对于增进我们对癌症生物学的理解和开发新的癌症治疗方法至关重要。在本研究中，我们发现Mn2处理导致肿瘤组织中KLRG1巨噬细胞（KLRG1 Mφ）显着增加，并且大多数这些细胞表现出M1表型。敲低巨噬细胞中的KLRG1不仅损害了它们诱导适应性免疫细胞下游抗肿瘤免疫的能力，而且损害了它们对肿瘤细胞的直接细胞毒性。此外，KLRG1巨噬细胞极化表型的变化进一步导致T细胞增殖和CD4 T细胞向Th1表型极化，从而为抗肿瘤免疫反应奠定了基础。我们的研究拓展了人们对Mn2抗肿瘤机制的认识，并首次证明Mn2可以调节KLRG1 Mφ的功能来参与抗肿瘤活性。这些发现表明 KLRG1 可能代表开发新肿瘤疗法的一个有前景的靶点。版权所有 © 2024。由 Elsevier B.V. 出版。

Manganese (Mn) play a crucial role in various biological processes in the body. Studies have primarily focused on their ability to enhance immune cell function and activation against tumors, particularly in dendritic cells (DCs), macrophages, and T cells. Tumor-associated macrophages (TAMs) are often the most abundant immune cell population present in the tumor microenvironment (TME). Thus, it would be valuable to investigate the mechanism by which Mn2+ regulates TAMs' involvement in anti-tumor immunity, as it be crucial for advancing our understanding of cancer biology and developing new treatments for cancer. Here, in the present study we discovered that Mn2+ treatment led to a significant increase in KLRG1+ macrophages (KLRG1+ Mφ) in tumor tissues, and most of these cells exhibited an M1 phenotype. Knocking down KLRG1 in macrophages not only impaired their ability to induce downstream anti-tumor immunity of adaptive immune cells, but also impaired their direct cytotoxicity against tumor cells. Moreover, the changes in the polarization phenotype of KLRG1+ macrophages further lead to T cell proliferation and the polarization of CD4+ T cells towards a Th1 phenotype, thereby establishing a foundation for the antitumor immune response. Our study expands the understanding of the anti-tumor mechanism of Mn2+ and demonstrates, for the first time, that Mn2+ can regulate the function of KLRG1+ Mφ to participate in anti-tumor activities. These findings suggest that KLRG1 may represent a promising target for developing new tumor therapy.Copyright © 2024. Published by Elsevier B.V.