Restoring anti-oncodriver Th1 responses with dendritic cell vaccines in HER2/neu-positive breast cancer: progress and potential

Abstract

HER2/neu is expressed in the majority of in situ breast cancers, but maintained in 20–30% of invasive breast cancer (IBC). During breast tumorigenesis, there is a progressive loss of anti-HER2 CD4pos Th1 (anti-HER2Th1) from benign to ductal carcinoma in situ, with almost complete loss in IBC. This anti-HER2Th1 response can predict response to neoadjuvant therapy, risk of recurrence and disease-free survival. Vaccines consisting of HER2-pulsed type I polarized dendritic cells (DC1) administered during ductal carcinoma in situ and early IBC can efficiently correct anti-HER2Th1 response and have clinical impact on the disease. In this review, we will discuss the role of anti-HER2Th1 response in the three phases of immunoediting during HER2 breast cancer development and opportunities for reversing these processes using DC1 vaccines alone or in combination with standard therapies. Correcting the anti-HER2Th1 response may represent an opportunity for improving outcomes and providing a path to eliminate escape variants.