PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients withbreast cancer: TNBC versus TPBC.

Abstract

Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating Tcells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade3 (72% versus 66.7%, P <0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus68.3%,P =0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P =0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P =0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.