Xiang Siyu, Yang Liu, He Yun, Ding Feng, Qiao Shuangying, Su Zonghua, Chen Zheng, Lu Aiping, Li Fangfei
Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Institute of Precision Medicine and Innovative Drug Discovery (PMID), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Cells. 2025 Jan 10;14(2):88. doi: 10.3390/cells14020088.
Alpha-1 antitrypsin (AAT) is a key serine protease inhibitor for regulating proteases such as neutrophil elastase. AAT restrains the pulmonary matrix from enzymatic degradation, and a deficiency in AAT leads to inflammatory tissue damage in the lungs, resulting in chronic obstructive pulmonary disease. Due to the crucial biological function of AAT, the emerging research interest in this protein has shifted to its role in cancer-associated inflammation and the dynamics of the tumor microenvironment. However, the lack of comprehensive reviews in this field hinders our understanding of AAT as an essential immune modulator with great potential in cancer immunotherapy. Therefore, in this review, we have elucidated the pivotal roles of AAT in inflammation and the tumor microenvironment, including the structure and molecular properties of AAT, its molecular functions in the regulation of the inflammatory response and tumor microenvironment, and its clinical implications in cancer including its diagnosis, prognosis, and therapeutic intervention. This review seeks to bridge the gap in the understanding of AAT between inflammatory diseases and cancer, and to foster deeper investigations into its translational potential in cancer immunotherapy in the future.
α-1抗胰蛋白酶（AAT）是一种关键的丝氨酸蛋白酶抑制剂，用于调节诸如中性粒细胞弹性蛋白酶等蛋白酶。AAT可抑制肺基质的酶解降解，而AAT缺乏会导致肺部炎症组织损伤，进而引发慢性阻塞性肺疾病。由于AAT具有关键的生物学功能，对该蛋白的新兴研究兴趣已转向其在癌症相关炎症和肿瘤微环境动态变化中的作用。然而，该领域缺乏全面的综述阻碍了我们将AAT理解为一种在癌症免疫治疗中具有巨大潜力的重要免疫调节剂。因此，在本综述中，我们阐明了AAT在炎症和肿瘤微环境中的关键作用，包括AAT的结构和分子特性、其在调节炎症反应和肿瘤微环境中的分子功能，以及其在癌症中的临床意义，包括诊断、预后和治疗干预。本综述旨在弥合炎症性疾病和癌症之间对AAT理解上的差距，并促进未来对其在癌症免疫治疗中转化潜力的更深入研究。
