97. Impact of psychological stress on the adaptive immune system and disease progression in a triple negative breast and a transgenic ovarian cancer mouse model

Abstract

Immune suppression plays a critical role in tumor progression, particularly in triple negative breast cancer (TNBC) and ovarian cancer. However the role of stress in adaptive immunity is still unclear. We hypothesize that psychological stress can regulate T cell mediated immunity, thus contributing to disease outcome. To test this hypothesis, we used female BALB/c mice injected with TNBC 4T1 mammary adenocarcinoma cells into the mammary fat pad and a LSLS-KrasG12D/+PtenloxP/loxp conditional transgenic mouse model for endometrioid ovarian cancer. For the TNBC model, mice were randomized into 4 groups (n = 10); (1) social isolation; (2) restraint stress for 1 h,3x/week; (3) restraint stress for 2 h, daily and (4) no stress. For the ovarian model, mice were restrained for 1 h,3x week. In the TNBC model, the stress groups demonstrated significantly reduced survival compared to non-stressed controls (p = 0.013) with none of the social isolation mice surviving. There was a significant difference across the groups for CD3 (p = 0.042), CD3CD69 (p = 0.047) and CD4FOXP3 (Tregs; p = 0.0014) in mouse spleens. In the ovarian mouse model, we found that stressed mice demonstrated early onset of tumors and a significant decrease in CD3CD69 (p = 0.006). These findings indicate that stress regulates T cell immunity in mice with TNBC and ovarian cancer and demonstrate the complexity of the stress response in tumor-bearing, immune competent mice.