Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages

抗体调理的肿瘤细胞的吞噬作用导致巨噬细胞中形成离散的液泡区室

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作者:Ramraj Velmurugan, Sreevidhya Ramakrishnan, Mingin Kim, Raimund J Ober, E Sally Ward

Abstract

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.

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