Tapping Into Innate Immunity to Reduce Breast Tumor Growth

Scientists from Dana-Farber Cancer Institute found that a compound that can reverse the function of innate immune system cells-to fight tumors rather than encourage growth-caused breast tumors in mice to shrink and withdraw from distant metastases. When combined with chemotherapy or another immunotherapy, the new compound significantly extended the period of tumor remission.

This study was first published in the journal Nature.

“Once they’ve undergone conversion, macrophages act as the orchestrators of the immune system attack on the tumor,” said Anthony Letai, MD, PhD, of Dana-Farber, co-author of the study in a news release. “Our findings demonstrate that class IIa HDAC [histone deacetylase] inhibitors can be an effective way of harnessing the antitumor potential of macrophages in cancer therapy.”

“The future of cancer treatment is likely to involve combinations of therapies that act on both the innate and adaptive arms of the immune system, as well as therapies, such as chemotherapy, radiation therapy, or targeted therapy, that act on cancer cells themselves,” Letai continued. “The ability to engage the innate immune system is an exciting new front in cancer therapy.”

Immunotherapy actually influences the behavior to T cells, the study’s lead author Jennifer Guerriero, PhD, of Dana-Farber, explains. “This strategy has been effective against several types of cancer, but generally only a subset of patients benefit. We wanted to see if harnessing both arms of the immune system could produce superior results.”

The targets of the study were tumor-associated macrophages (TAMs). They’re often found deeply embedded within tumors, but although they’re part of the immune system, they frequently promote tumor growth. In doing so, they’re responding to cues issued by the tumor itself.

A selective, first-in-class, class IIa HDAC inhibitor, TMP195 switches the macrophage response by altering gene activity within TAMs. For this particular study, TMP195 reduced the rate of tumor growth in mice with breast tumors. Combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumor reduction. These data introduce class IIa HDAC inhibition as a means to harness the antitumor potential of macrophages to enhance cancer therapy.

This may be the cusp of using both areas of the immune system for future cancer therapies, thus helping a subset of patients who require treatment that is successful for them.