Epigenetic Modulation, Checkpoint Inhibition Showed Potential in HER2 Breast Cancer
Previous studies suggest that epigenetic modulation can change the breast tumor microenvironment.
|The following article features coverage from the 2017 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas. Click here to read more of Oncology Nurse Advisor's conference coverage.|
A combination of checkpoint inhibition and epigenetic modulation improves survival and supports tumor suppression in a HER2+ mouse model of breast cancer, according to Johns Hopkins University researchers, who presented their study findings at the 2017 San Antonio Breast Cancer Symposium (SABCS 2017).
Checkpoint inhibition is a successful therapy for naturally immunogenic cancers. However, most breast cancers are not highly immunogenic and lack tumor antigen expression and recognition. Previous studies suggest that epigenetic modulation can transform breast tumor microenvironment by stimulating the activation and trafficking of myeloid derived suppressor cells (MDSCs) that change immunogenicity and sensitize tumors to checkpoint inhibition.
The researchers tested the efficiency of combined epigenetic modulation and checkpoint inhibition using the histone deacetylase inhibitor ENT and antibodies for 2 checkpoint inhibitor proteins, a-PD-1 and a-CTLA-4. A combination of ENT with either checkpoint inhibitor significantly improved survival and delayed tumor growth. It also increased the infiltration of granulocytic-MDSCs into the tumor microenvironment, with a significant increase in T cell activation, exhaustion, and myeloid function. However, the pathway behind this observation remains undiscovered.
“It is our hope that these novel findings will provide further rationale for combination therapy and improve the response rate of these immune therapies in patients with breast cancer,” noted the researchers.
Roussos Torres ET, Ma H, Christmas B, et al. Combination checkpoint inhibition and epigenetic modulation promotes tumor suppression and improves survival in HER2+ models of breast cancer. Poster Presentation at: 2017 San Antonio Breast Cancer Symposium; December 6-9, 2017; San Antonio, TX. Abstract P1-08-01.