New insights on how immune cells are recruited and reprogrammed to drive tumor development
Researchers at Karolinska Institutet show how a certain type of immune cells, macrophages, can be recruited into breast cancer tumors, where they are reprogrammed to support and drive tumor growth. In a study published in the scientific journal PNAS, they describe that low levels of the tumor suppressor protein TAp73 lead to hyperactivation of NFkB signaling and an inflammatory condition in breast cancer as well as secretion of molecules that recruit tumor-promoting macrophages into the tumor.
Breast cancer is one of the most common cancers worldwide and understanding this complex disease is therefore of great importance.
"Previous studies have shown that infiltration of immune cells into tumors is of great importance for how the tumor develops and that there is a fine balance between infiltration of immune cells that attack the tumor cells and immune cells that can instead protect the tumor cells and help the tumor grow and spread," says Margareta Wilhelm, researcher at the Department of Microbiology, Tumor and Cell Biology, and corresponding author of the article.
"In the study we report that decreased levels of the protein TAp73 correlate with more aggressive types of breast cancer and that TAp73 acts as an inhibitor of NFkB activation. NFkB activates a variety of functions in the cell including the secretion of chemokines that attract immune cells into the tumor," she continues.
"Downregulation or lack of TAp73 leads to a condition in which NFkB is hyperactivated and upregulates secretion of the chemokine CCL2 which attracts circulating monocytes into the tumor where they differentiate into a special type of macrophage that supports tumor growth and leads to a more aggressive disease."
The published study increases the understanding of the mechanisms that drive the development of breast cancer and identifies TAp73 as an important factor in regulating how immune cells are recruited to the tumor.
More information: Johanna Wolfsberger et al. TAp73 represses NF-κB–mediated recruitment of tumor-associated macrophages in breast cancer, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2017089118