Immunologists have discovered a mechanism through which immune cells get recruited into breast cancer tumors, and instead of destroying malignant cells, immune cells are reprogrammed to help cancer grow.
“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,” explained Margareta Wilhelm, the corresponding author of the article published in PNAS.
Wilhelm and colleagues sought to unravel the mechanisms through which phagocytic immune cells called macrophages end up protecting tumor cells rather than attacking them.
The team identified that low levels of TAp73, a tumor-suppressing protein, are associated with more aggressive forms of breast cancer. TAp73 normally suppresses inflammation by inhibiting NFkB. The dip in TAp73 levels in tumors results in a surge of inflammatory signals.
“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,” said Wilhelm.
Estimates suggest 1 in 8 women in the U.S. will develop breast cancer throughout their lifetimes. These findings deepen our understanding of how tumors modulate inflammation and evade capture by the immune system, paving the way for therapeutic countermeasures to reverse them.
Sources: Clinical Cancer Research, Karolinska Institute.