15357163mct150335-sup-148428_2_video_3475451_76ky0y.avi (2.3 MB)

Movie S6 from Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells

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posted on 2023-04-03, 15:21 authored by Ramraj Velmurugan, Dilip K. Challa, Sripad Ram, Raimund J. Ober, E. Sally Ward

MUM images of trogocytic tubules.The movie corresponds to Figure 4B. Images of trastuzumab (left panels) or trastuzumab and MEM-GFP (red and green, respectively; right panels) from the cameras set at focal planes of ~ 1.2 Âµm and 1.8 Âµm in the MUM configuration are displayed. The cyan line in the left panels indicates the approximate edge of the macrophage, obtained by averaging and thresholding the MEM-GFP images. The movie pauses for 2 seconds at different timepoints to indicate the same features of the tubulation process (yellow arrows) presented as individual frames in Figure 4B. Time on the upper left is shown in minutes:seconds format. The movie plays at a speed of 27x real-time. Scale bar = 5 Âµm.

Funding

Cancer Prevention and Research Institute of Texas

NIH

History

ARTICLE ABSTRACT

Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcγ receptor (FcγR)–mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells. Further, antibody engineering to increase FcγR interactions enhances this tumoricidal activity. These studies extend the complex repertoire of activities of macrophages to trogocytic-mediated cell death of HER2-overexpressing target cells and have implications for the development of effective antibody-based therapies. Mol Cancer Ther; 15(8); 1879–89. ©2016 AACR.