Triple negative breast cancer (TNBC) is the breast cancer subtype associated with the poorest outcomes due to a high propensity for recurrence and lack of biological targets. Trastuzumab emtansine (T-DM1 or Kadcyla™), a novel antibody–drug conjugate, has been an outstanding new therapy for human epidermal growth factor receptor 2 amplified (HER2-positive) breast cancer patients owing to its ability to prolong progression-free and overall survival in patients refractory to other HER2-directed therapies, together with its favourable safety profile. Here we investigated the therapeutic potential and the immunological mode of action of TDM-1 treatment alone or in combination with immune checkpoints in TNBC tumours with low (+1IHC) to medium (+2IHC) levels of HER2 expression. We found that T-DM1 was able to reduce the growth of TNBC tumours with +1IHC levels of HER2 and shows a potent anti-proliferative activity in TNBC tumours with +2IHC HER2 levels in vivo. Accordingly, T-DM1 induces an efficient anti-tumour immune response in TNBC tumours +2IHC HER2. Furthermore, T-DM1 treatment increases the immunogenicity of TNBC +2IHC HER2 tumours in vivo, induces the intratumoral recruitment of tumour infiltrating lymphocytes(TILs) including CD4+and CD8+Tcells, as well as it induces the production of cytokines and chemokines. Importantly, T-DM1 elevate markedly the expression of immune checkpoints such us CTLA-4 and PD1 on TILs of both TNBC tumours with low to meduim HER2 levels. Our finding provide a rational to combine T-DM1 treatment with immunotherapeutic strategies and indicate that T-DM1 is effective at eliciting anti-tumour immunity that might render TNBC tumours with low HER2 levels susceptible to the checkpoint blockade. Subsequently, we are currently evaluating the synergistic effect of the combination therapy which may be a promising new therapy for TNBC with low HER2 expression.