Association of allograft rejection response score with biological cancer aggressiveness and with better survival in triple-negative breast cancer (TNBC)

561 Background: Although the importance of immunity in the progression of breast cancer was widely reported, the clinical relevance of enhanced immune response is still unclear. We hypothesized that the enhanced immune response is associated with better breast cancer patient survival. Methods: We used 6,245 breast cancer patient sample data from publicly available data sets (METABRIC, GSE96058, TCGA cohorts). To elucidate the function of immunity in breast cancer, we calculated the immune function score using hallmark allograft rejection gene sets by Gene Set Variation Analysis algorithm. Results: The immune response score correlated most with cytolytic activity among hallmark immune-related gene sets in both cohorts (Spearman’s rank correlation (r) = 0.892 and 0.860, respectively, both p < 0.01). The score reflected the amount of infiltrating immune cells, including several anti-cancer immune cells (CD8+ T cells, CD4+ memory T-cells, T helper Type 1 cells, M1 macrophages, plasmacytoid dendritic cells), T helper Type 2 cells, and B cells. The score also correlated with expression levels of immune checkpoint molecule genes (all r > 0.500). A high score was significantly associated with high intratumor heterogeneity, homologous recombination deficiency (HRD), and mutation rate in the TCGA cohort (all p < 0.001). A high score was significantly associated with advanced Nottingham histological grade, advanced stage, and lymph node metastasis. High score breast cancer enriched not only immune-related gene sets but also pro-cancer-related gene sets, such as epithelial-mesenchymal transition (EMT) and p53 pathway, in both ER-positive/HER2-negative breast cancer and TNBC. The score was highest in TNBC compared to other subtypes, and TNBC with high score was significantly associated with better survival. Conclusions: The counterbalance between malignant biology and the enhanced immune response is an important factor in clinical outcomes.