Gurung Jampa Lhamo, Tamang Raju Lama, Madduri Lepakshe, Bennett Robert G, Harris Edward N, Denton Paul W, McVicker Benita
Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biology (Basel). 2025 Sep 5;14(9):1198. doi: 10.3390/biology14091198.
Stabilin-1 (STAB1) is a multifunctional scavenger receptor expressed by endothelial cells of the liver, spleen, lymph nodes, bone marrow and a subset of macrophages. STAB1 interacts with different ligands and modulates a wide range of functions including cell trafficking, endocytosis, homeostasis, angiogenesis, and tumor vascularization. The role of STAB1 in cancer progression and metastasis first became evident in knockout (KO) mice, which developed smaller primary tumors and metastatic foci for some cancers. To date, various clinical cohorts and preclinical rodent studies have shown that STAB1 inhibition is associated with elevated anti-tumor T-cell responses. Moreover, human trials using anti-STAB1 antibody treatment indicate a shift towards immune activation and the potential to overcome cancer treatment resistance experienced with other immunotherapies. Although the role of STAB1 in cancer development and metastasis remains to be defined, STAB1 signaling in tumor-associated macrophages and downstream immune modulation are thought to be crucial mechanisms. Herein, we discuss the role of STAB1 in tumor-associated macrophages in relationship to disease progression and patient outcome.
稳定素-1(STAB1)是一种多功能清道夫受体,由肝脏、脾脏、淋巴结、骨髓的内皮细胞以及一部分巨噬细胞表达。STAB1与不同的配体相互作用,并调节多种功能,包括细胞运输、内吞作用、体内平衡、血管生成和肿瘤血管形成。STAB1在癌症进展和转移中的作用首先在基因敲除(KO)小鼠中变得明显,这些小鼠某些癌症的原发性肿瘤和转移灶较小。迄今为止,各种临床队列研究和临床前啮齿动物研究表明,抑制STAB1与抗肿瘤T细胞反应增强有关。此外,使用抗STAB1抗体治疗的人体试验表明,会朝着免疫激活方向转变,并且有可能克服其他免疫疗法所经历的癌症治疗耐药性。尽管STAB1在癌症发展和转移中的作用仍有待确定,但肿瘤相关巨噬细胞中的STAB1信号传导和下游免疫调节被认为是关键机制。在此,我们讨论STAB1在肿瘤相关巨噬细胞中与疾病进展和患者预后相关的作用。