The combined presence of CD20+B cells and PD-L1+tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

Purpose The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples. Methods PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1(+) tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1(+) TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. Results PD-L1(+) tumor cells, PD-L1(+) TILs, and CD20(+) TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1(+) tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20(+) TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1(+) TILs strongly correlated with high TILs, CD20(+) TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20(+) TILs and PD-L1(+) TILs (CD20(+)TILs/PD-L1(+)TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20(+) TILs or PD-L1(+) TILs alone. In multivariate analyses, CD20(+)TILs/PD-L1(+)TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37-0.77) and TN IBC (HR: 0.39 95% CI 0.17-0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43-0.85) and TN IBC (HR: 0.38 95% CI 0.17-0.83). Conclusion CD20(+)TILs/PD-L1(+)TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.