Abstract P5-01-12: Prognostic implications of tumor-infiltrating lymphocytes (TIL) in association with PD-L1 expression, and serum cytokine levels in early breast cancer

Abstract Background Immune system has been known to influence the prognosis of breast cancer (BC). However, the relationship between immune modulating factor (PD-L1) and tumor infiltrating lymphocyte (TIL) profiles in breast cancer has yet to be revealed according to breast cancer subtypes. In addition, the effects of circulating cytokines on TILs have not been addressed. Patients and methods We investigated the relationship between the profiles of TILs and PD-L1 expression of the primary tumor tissue by immunohistochemistry with clinical outcomes in 253 patients who underwent surgery for early breast cancer at National Cancer Center from January 2001 to December 2005. Besides, the serum cytokines including IL-10, IL-18, IL-6, IFN-g, and TGF-β1 were measured at diagnosis. Clinical data including hormone receptors status, HER2 expression, disease free survival (DFS), and overall survival (OS) were collected. Results Median age of patients was 49 years (range, 32-74) and median follow-up was 8.5 years. One hundred eighty five (73.1%) patients had hormone receptor (HR) positive and 101 (39.9%) patients had node positive BC. CD8+ TILs were more abundant in low PD-L1 expressed tumor (P = 0.027), though there was no association between FOXP3+ TILs and PD-L1 expression (P = 0.585). A total number of TILs was higher in HR negative compared with HR positive BC (P = 0.061) and the expression of PD-L1 was more frequent in HR positive BC (P<0.001). In HR negative BC, there was a trend of longer DFS in patients with higher CD8+ TILs and low PD-L1 expression (P = 0.097). However, such association was not detected in HR positive BC patients. Among serum cytokines we examined, the higher levels of IL-18 were significantly associated with shorter DFS in HR negative BC (P = 0.006). In HR negative BC, higher CD8+ TILs with low PD-L1 expression and lower IL-18 were significantly related with better clinical outcomes when adjusted with other clinical factors (DFS, P = 0.032; OS, P = 0.048). Conclusions Lower PD-L1 expression in breast tumor was associated with higher CD8+ lymphocyte infiltration. Especially in HR negative BC, increasing CD8+ TILs with lower PD-L1 expression and lower serum IL-18 level were good prognostic factors. Further validation will be needed to establish the role of immune profiles in BC patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-12.