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

The immune checkpoint protein B7H4 plays an important role in the positive as well as the negative regulation of immune Tcell responses. When expressed on cancer cells, B7H4 inhibits Tcell activity, and numerous types of cancer cells use upregulation of B7H4 as a survival strategy. Thus, B7H4 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 B7H4 interactors, are controversial. In particular, the cisinteractors of B7H4 on cancer cell plasma membranes have not been investigated to date. The present study used a proteomic proximitylabelling assay to investigate the molecular neighbours of B7H4 on the surface of the human breast cancer cells SKBR3. By comparison to a comprehensive proteome analysis of SKBR3 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 B7H4 on cancer cells.