Immuno-oncology in triple-negative breast cancer

Abstract

The immune system plays an important role in breast cancer. Triple-negative breast cancer (TNBC) has a higher mutational load compared to other subtypes. In addition, higher levels of tumor-associated antigens suggests that immunotherapies are a promising treatment option especially for TNBC. Our review discusses both the complexity of the immune system and the cancer immune-cell cycle. In fact, a higher level of tumor-infiltrating lymphocytes is associated with an improved prognosis as well as a better response to chemotherapy in TNBC. Important target structures within the cancer immune-cell cycle are the so-called "immune checkpoints". Immune checkpoint inhibitors (ICPi) block the interaction of certain cell surface proteins that serve as "brakes" of immune reactions. Recent studies have shown ICPi improved survival in early as well as advanced TNBC. However, this has the price of increasing, mainly, immune-mediated toxicity. ICPi strengthen tumor-specific T cell-mediated immunity by "releasing the brake" of the immune system. In combination with chemotherapy, ICPi are already approved for TNBC. As a further step, individualized vaccination strategies against tumor-associated neoantigens represent another promising approach. A liposome-formulated intravenous RNA vaccine encoding different tumorassociated antigens is currently being studied in TNBC and leads to neoantigen-specific immune responses. These novel strategies will improve the prognosis of patients with triple-negative breast cancer.

Targeted Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight on Pembrolizumab

“…TNBC has been considered to have the highest immunogenic potential of all breast cancers, with enrichment for BRCA germline mutations and higher somatic mutational load and tumor-associated neoantigens, but are rarely associated with microsatellite instability. 39 , 40 Thus, TNBC is a target for immune-modulating therapies. 41 Early- and advanced-stage breast cancers differ in their tumor and immune cell microenvironments that may impact immunogenicity and offer therapeutic opportunities for the incorporation of checkpoint inhibitors.…”