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Identification of the cis-molecular neighbours of the immune checkpoint protein B7-H4 in the breast cancer cell-line SK-BR-3 by proteomic proximity labelling

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Rees, Johanna 


The immune checkpoint protein B7-H4 plays an important role in the positive as well as the negative regulation of immune T-cell responses. When expressed on cancer cells, B7-H4 inhibits T-cell activity, and numerous types of cancer cells use upregulation of B7-H4 as a survival strategy. Thus, B7-H4 is a potential target for anticancer drug therapy. Unfortunately, the cell biology of this molecule has yet to be fully elucidated. Even basic properties, such as the nature of B7-H4 interactors, are controversial. In particular, the cis-interactors of B7-H4 on cancer cell plasma membranes have not been investigated to date. The present study used a proteomic proximity-labelling assay to investigate the molecular neighbours of B7-H4 on the surface of the human breast cancer cells SK-BR-3. By comparison to a comprehensive proteome analysis of SK-BR-3 cells, the proximity method detected a relatively small number of low abundance plasma membrane proteins highly enriched for proteins known to modulate cell adhesion and immune recognition. It may be inferred that these molecules contribute to the immunosuppressive behaviour that is characteristic of B7-H4 on cancer cells.



specific proteomic proximity labelling assay using tyramide, proteomics, B7-H4, microenvironment, integrins, HLA class I histocompatibility antigen α chain E, Breast Neoplasms, Cell Adhesion, Cell Line, Tumor, Cell Membrane, Cell Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Immune Checkpoint Inhibitors, Lymphocyte Activation, Protein Interaction Mapping, Protein Interaction Maps, Proteomics, T-Lymphocytes, Up-Regulation, V-Set Domain-Containing T-Cell Activation Inhibitor 1

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International Journal of Oncology

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Demetrios A. Spandidos Ed. & Pub.
Wellcome Trust (108467/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/J021091/1)
Biotechnology and Biological Sciences Research Council (BB/H024085/1)
BBSRC Astra Zeneca (formerly MedImmune)