CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1

More than 70% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7-H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Among those, tumor-associated macrophages can comprise up to 50% of the tumor mass and are thought to support tumor growth through various mechanisms. However, a lack of information on CD276 function and interaction partner(s) impedes rigorous evaluation of CD276 as a therapeutic target in oncology. Therefore, we aimed to understand the relevance of CD276 in tumor-macrophage interaction by employing a 3D spheroid coculture system with human cells. Our data show a role for tumor-expressed CD276 on the macrophage recruitment into the tumor spheroid, and also in regulation of the extracellular matrix modulator PAI-1. Furthermore, our experiments focusing on macrophage-expressed CD276 suggest that the antibody-dependent CD276 engagement triggers predominantly inhibitory signaling networks in human macrophages.

Automated summary

CD276, a potential immune checkpoint family member, is expressed in over 70% of colorectal, prostate, ovarian, pancreatic, and breast cancer specimens, with high expression correlating with poor clinical prognosis. Lack of information on CD276 function and interaction partners hinders its rigorous evaluation as a therapeutic target in oncology. Experimental data suggest that tumor-expressed CD276 plays a role in macrophage recruitment and regulation of the extracellular matrix, while macrophage-expressed CD276 triggers inhibitory signaling networks.