Abstract
BACKGROUND: Expression of PD-L1 has been estimated to predict the therapeutic potential of PD-L1 inhibition in solid tumors. Recent studies have demonstrated that PD-L1 plays a critical role in regulatory T-cell (Treg) development and functional maintenance. Although increases in FOXP3(+)Treg infiltration and PD-L1 expression have been revealed in several malignancies, their correlation in human breast tumors is as yet unclear. METHODS: Whole-tissue sections from 501 patients with breast cancer were examined for PD-L1 and FOXP3 expression by immunohistochemistry. Correlation between their expressions and the association with clinicopathological features, intrinsic tumor subtypes and patient's prognosis were studied. RESULTS: PD-L1 expression and FOXP3(+)Treg infiltrates in tumor tissue demonstrated a high correlation (rs =0.334, p<0.001) in this cohort of breast cancer patients. High PD-L1 expression and increased FOXP3(+)Treg infiltrates were both associated with high histological grade, negative ER and PR status, and aggressive intrinsic tumor subtypes, especially the basal-like subtype. Tumors with concomitant high expressions of the two markers had the worst prognosis. Multivariate analysis proved both markers to be the independent predictors for decreased overall survival of patients, particularly in the basal-like subtype. CONCLUSIONS: The results suggest that PD-L1 and FOXP3(+)Tregs may work synergistically and their up-regulated expressions promote tumor immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming on blocking PD-L1 and depleting Tregs might improve therapeutic efficacy in breast cancer patients, especially those with basal-like carcinoma.