Poster Presentation 28th Lorne Cancer Conference 2016

Combined chemotherapy and immunotherapy in triple negative breast cancer (#287)

Chenhao Zhou 1 2 , Phillip Darcy 2 , Sherene Loi 1
  1. Translational Breast Cancer Genomics and Therapeutics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria , Australia
  2. Immunotherapy Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

Triple negative breast cancer (TNBC) is associated with worse clinical outcomes compared with other subtypes of breast cancer. Current treatments for TNBC are limited by the lack of therapeutic targets. Recently, the role of platinum agents such as carboplatin has been studied, and has shown promising results in clinical trials, although not all TNBC patients respond. Strong responses to carboplatin were found in TNBC patients with a high level of tumour infiltrating lymphocytes (TILs), suggesting an interaction between carboplatin and host immunity. We hypothesized that carboplatin can modulate immunity, and that combining carboplatin with immunotherapy may have a synergistic therapeutic effect against TNBC. Using the syngeneic AT3ova tumour cell line, we investigated whether carboplatin can induce immune activation in vitro and in vivo, and whether the addition of immunotherapy (PD1 blockade) could further enhance the efficacy of carboplatin. We have demonstrated that carboplatin could inhibit growth of AT3ova cells and increased their immunogenicity with respect to immune markers (MHC I, MHC II, CD80), and enhanced the function of CD8 T cells as indicated by increased IFNγ production. Increased expression of the immune checkpoint molecule PD1 on CD8 T cells provided the rationale to combine checkpoint inhibitor anti-PD1 monoclonal antibody (mAb) with carboplatin. Consequently, we found that combined therapy had enhanced efficacy in inhibiting growth of AT3ova tumours, compared to carboplatin therapy alone. We demonstrated that combined therapy had enhanced effects in inducing the immunogenicity of AT3ova cells and CD8 T cells, as well as increasing the percentage of CD8 T cells within the tumour microenvironment. In summary, we found that carboplatin can effectively induce anti-tumour immunity, and combining PD1 blockade with carboplatin could further augment anti-tumour immunity, leading to an enhanced therapeutic response. This study highlights the potential of combined chemo- and immunotherapy therapy for treatment of TNBC.