CCL5 expression and tumor infiltrating immune cells in triple negative breast cancer.
11553 Background: CCL5 is a chemo-attractant of regulatory T cells, promoting tumor immune avoidance and related to a poor outcome in several malignancies; however, in triple negative breast cancer (TNBC), it is related to a better outcome. Our aim was to evaluate the correlation between CCL5 and tumor infiltrating immune cells and their prognosis value. Methods: We evaluated 72 TNBC patients with residual disease after neoadjuvant chemotherapy with matched data of tumor infiltrating lymphocytes (TILs) count and CCL5 expression (profiled with NanoString). CCL5 expression levels were log2 transformed and median centered. Correlation between TILs (log2 transformed) and CCL5 was evaluated with the Spearman’s rank test. Cox PH model was used to investigate the effect of CCL5 (median as cutoff) and TILs ( < 20% and ≥20%) in distant-recurrence free survival. We used the CIBERSORT platform to evaluate the immune cells composition according to the expression of CCL5 (higher vs. lower or equal than median) in 3 independent TNBC datasets (GSE25066, GSE58812 and GSE76124). Results: There was a significant correlation between TILs and residual tumor size (P = 0.017) and CCL5 (ρ = 0.347, P = 0.003). In univariate analysis, TILs (HR = 0.276, 95%IC: 0.128-0.593; P = 0.001) and CCL5 (HR = 0.401; 95%CI: 0.206-0.781; P = 0.007) were both associated with outcome. In a multivariate analysis with CCL5 expression and TILs count, TILs was the only significant marker with a P = 0.008 (HR = 0.336; 95%CI: 0.150-0.753), in contrast to CCL5 (HR = 0.573; 95%CI: 0.285-1.154; P = 0.124). CIBERSORT analysis suggested that high CCL5 expression is associated with recruitment of CD8 cells (13% v 6%, P < 0.001; 6% v 1%, P < 0.001 and 12% v 8%, P = 0.003), activated CD4 memory T cells (4% vs. 2%, P < 0.001; 5% vs. 0%, P < 0.001; 3% vs. 0%, P < 0.001) and Macrophages M1 (9% vs. 7%, P = 0.022; 13% vs. 8%, P = 0.005; 11% vs. 5%, P < 0.001) in GSE25066, GSE58812 and GSE76124 datasets, respectively. Conclusions: TILs was the stronger and more significant prognostic immunological marker, even than CCL5 expression. High CCL5 expression was associated with enrichment of CD8 cells, activated CD4 memory T cells and Macrophages M1. Role of these cells in TNBC should be explored more deeply.