About 15% of breast cancers are classified as triple-negative, lacking receptors for estrogen, progesterone and Her2. These cancers do not respond to targeted hormonal therapies and tend to be particularly aggressive. Researchers had observed that triple-negative breast cancer (TNBC) patients who had higher numbers of a type of immune cell called myeloid-derived immunosuppressor cells (MDSCs) in their bloodstream had poorer outcomes.

A new report led by the School of Veterinary Medicine’s Rumela Chakrabarti, an assistant professor of biomedical sciences, and Sushil Kumar, a postdoctoral researcher in Dr. Chakrabarti’s lab, fills in crucial details about the connection between MDSCs and aggressive disease. In the Journal of Clinical Investigation, Dr. Chakrabarti’s team identified a protein, deltaNp63, on tumor cells that directs MDSCs to the tumor and metastatic sites. Blocking either this protein or the MDSCs themselves reduced tumor growth and metastasis in a mouse model of TNBC.

“We’re excited because we think our findings could make a big difference for triple-negative breast cancer patients,” said Dr. Chakrabarti. “Not only can deltaNp63 be used as a biomarker to help personalize treatment regimens, but targeting it may also provide an additive treatment for triple-negative breast cancer, in addition to chemotherapy and radiation.”

Dr. Chakrabarti’s team found deltaNp3 was elevated in samples of TNBC patient’s primary tumors, as were numbers of MDSCs. When they manipulated the level of deltaNp63, they found lower levels corresponded with less metastasis to distant tissues. Knocking down levels of deltaNp63 made the tumors much less aggressive, and it reduced numbers of MDSCs recruited to the tumor but not other immune cell types.

The Penn researchers also showed that blocking two signaling molecules activated by the deltaNp63 reduced metastasis and blood-vessel growth associated with tumor growth, while increasing levels of these signaling molecules caused MDSCs to boost the secretion of pro-tumor growth factors.

Dr. Chakrabarti believes that a drug that zeroes in on MDSCs could fill a gap in triple-negative breast cancer treatment. Offered in conjunction with more general therapies such as chemotherapy and radiation, it may give patients an option that is more tailored to their cancer. Her lab is now working with animal models and cell lines derived from breast-cancer patients to test this combination approach to treatment.