Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, Texas.
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, Texas.
Traffic. 2018 Apr;19(4):273-284. doi: 10.1111/tra.12552.
Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome. Furthermore, the size of the phagosome-associated vacuole is increased by inhibition of the mTOR pathway. Collectively, the identification of this vacuolar compartment has implications for understanding the subcellular trafficking processes leading to the destruction of phagocytosed, antibody-opsonized cancer cells by macrophages.
尽管基于抗体的治疗药物在治疗癌症方面的应用迅速扩大，但对于吞噬抗体包被的肿瘤细胞后细胞内过程的了解仍很有限。本文报道了在存在 HER2 特异性抗体曲妥珠单抗的情况下，HER2 阳性癌细胞被吞噬后，巨噬细胞中观察到的与吞噬体相关的空泡的形成。我们证明，该空泡是一种独特的细胞器，与吞噬体紧密相邻。此外，通过抑制 mTOR 通路，可使与吞噬体相关的空泡的体积增大。总的来说，这种空泡结构的确立对于理解导致巨噬细胞吞噬和抗体包被的肿瘤细胞被破坏的细胞内转运过程具有重要意义。
