fig3

Figure 3. Immune regulation in HER2+ breast cancer. Immunomodulation of lapatinib-resistant HER2+ breast cancer cells act through the expression of PD-L1 by cancer cells which inhibits the cytotoxic activity of CD8+ lymphocytes. Different compounds acting on HER2- or HER2-signaling partners for clinically or preclinical agents are shown in yellow boxes. Main inhibitors target: (1) HER2 or HER2/HER3 and HER2/EGFR receptors; (2) CTLA-4 inhibitors that target CTLA-4 on lymphocytes; (3) PD-L1 inhibitors that target PD-L1 on cancer cell; or (4) PD-1 inhibitors that target PD-1 on lymphocyte. Images were created using Biorender.com. HER2: human epidermal growth factor receptor 2; HER3: human epidermal growth factor receptor 3; CTLA-4: cytotoxic T-lymphocyte antigen 4; CTL: cytotoxic T-lymphocyte; DC: dendritic cell; MHC: major histocompatibility complex; PD-1: programmed cell death-1; PD-L1: programmed cell death-1 ligand; TCR: T cell receptor; Tregs: regulatory T cells; EGFR: epidermal growth factor receptor; T-DM1:trastuzumab emtansine DM1