Progress and challenges of immunotherapy in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC), a subtype of breast cancer, is defined as lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression. Compared with other subtypes in breast cancer, TNBC is more likely to recur and metastasize, with a lower survival rate. Due to the absence of definitive targets, there was limited novel therapeutic interventions and chemotherapy remained the primary treatment in the past decades. Following the development of immune checkpoint inhibition (ICI) in solid tumors and validation of the immunogenicity in TNBC, immunotherapy has attracted more and more attentions. On basis of accumulating clinical studies, we reviewed the current progress targeting different immune checkpoints in several-lines treatment for TNBC, including programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) inhibitor, and other novel immunotherapeutic approaches (e.g., individualized peptide vaccine, cancer-testis antigen (CTA), new antigen vaccine, RNA vaccine and chimeric antigen receptor modified T cells (CAR-T)). In order to improve the survival outcome of TNBC populations, we further discussed potential predictive biomarkers for immunotherapy (e.g., PD-L1 expression, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), microsatellite instability (MSI)/mismatch repair (MMR) deficiency) and challenges in the future treatment of TNBC.

Keywords: CAR-T; CTLA-4; Immunotherapy; MSI/MMR; PD-1/PD-L1; TILs; TMB; Triple-negative breast cancer; Vaccine.