Tumor Immune Microenvironment in Humanized NSG-SGM3 Mice with Breast Cancer Undergo HER2 Chimeric Antigen Receptor T Cell Therapy

Breast cancer (BC) is one of the leading causes of death in women and current treatment options are not always the most effective or efficient when treating this disease. Chimeric antigen receptor (CAR) T cell therapy has therapeutic potential but faces challenges when controlling solid breast cancer tumor growth due to tumor immune microenvironment (TIME). Thus, our collaborators have designed novel CAR T cells simultaneously targeting tumor receptor HER2 and the myeloid cell receptor TNF-related apoptosis-inducing ligand receptor 2 (TR2). Here, we performed multicolor immunofluorescence staining on tumors from hNSG-SGM3 mice that had received different CAR T cell constructs. We found that by targeting HER2 and TR2, there was an increase in the number of T cells and a decrease of myeloid cells intratumorally. Many of the T cells expressed PD1, which could indicate recognition of target antigen. However, tumor volume was not controlled by this therapy which could be due to exhaustion and further analysis could be done to determine this. Thus, this study gave us a closer look at the interactions within the tumor immune microenvironment and our model will allow us to design a more effective CAR-T cell treatment in further studies.