近来的研究显示肿瘤微环境中免疫炎性细胞的代谢异常对其功能产生了关键的影响。我们前期建立了人源化的炎症微环境乳腺癌模型，发现微环境中肿瘤相关巨噬细胞glucose-serine-glycine-1-carbon代谢通路存在显著的异常。在此基础上，本研究将通过代谢组、肿瘤免疫学等手段，研究乳腺恶性进展不同阶段巨噬细胞存在的上述代谢异常及其影响巨噬细胞功能的分子机理，发现巨噬细胞以上述代谢相关代谢分子为介质的调控信号对肿瘤细胞及微环境内其他免疫细胞功能的影响，阐明乳腺癌恶性进展过程中的微环境内调控巨噬细胞上述代谢异常的信号通路及分子机制。本研究将有助于深化对肿瘤恶变过程各个阶段巨噬细胞代谢关键调控节点的认识，探讨相关代谢异常作为疾病进程的标志物和基于关键代谢调节分子的靶向治疗策略，为我们开发针对肿瘤炎性微环境，确定疾病进程的分子标志物和逆转恶性进展的靶向药物提供关键理论基础。

The development and outcome of malignant disease are determined by the inflammatory cell function and its interaction with host cells. Recent studies have shown that metabolic disorder in inflammatory cell has critical influence on its function in the cancer microenvironment. Previously we generated a humanized mouse model for studying the inflammatory microenvironment of breast cancer, and found glucose-serine-glycine-1-carbon metabolism of macrophages differed significantly in different inflammation types. Based on these results, we will explore the glucose-serine-glycine-1-carbon metabolic alterations of macrophages during breast cancer development and the regulatory machinery by which the metabolic disorder is controlled, uncovering the signaling pathway mediated by metabolites between macrophage and other inflammatory cells as well as tumor cells, and elucidating the metabolism regulatory networks and machineries in breast cancer development. The successful completion of this project will deepen our understanding of the metabolic regulatory nodes of macrophage in breast development, and establish the basis of developing metabolic biomarkers for disease progression, as well as therapeutic targets towards microenvironment to reverse the malignant progression.