Prognostic Significance of Programmed Death Ligand 1 Expression and Tumor-Infiltrating Lymphocytes in Axial Osteosarcoma

Abstract

To characterize the intratumoral immune microenvironment and evaluate its clinical implications in patients with primary axial osteosarcoma. Immunohistochemistry was used to interpret tumor programmed death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) profile of cluster of differentiation 8 (CD8), PD-L1, and programmed death 1 (PD-1) within 69 tumor specimens. Overall, all tumor specimens presented lymphocytic infiltrates, with PD-L1+ TILs being the most common subset (mean, 215.1 per slide mm2). Positive tumor PD-L1 expression was presented in 43.5% of tumors. Moderate to strong relationships were detected among TILs subsets and tumor PD-L1 expression. In addition, the density of PD-L1+ TILs was significantly correlated with favorable clinicopathologic features, including earlier Enneking stage. The positivity of tumor PD-L1 expression was associated with the tumor site and pathologic grade (P= 0.021 and 0.037, respectively). In univariate survival analysis, the high density of PD-L1+ TILs or CD8+ TILs was significantly correlated with both prolonged event-free survival and overall survival (OS), whereas the high infiltration of PD-1+ TILs was significantly associated with reduced OS, as was the positive tumor PD-L1 expression. Furthermore, multivariate analysis showed that CD8+ TILs and PD-L1+ TILs remained their significance for both event-free survival (P= 0.012 and 0.004, respectively) and OS (P= 0.033 and 0.002, respectively). However, both PD-1+ TILs and tumor PD-L1 expression failed to reach significance for OS. Our results suggested that the immune microenvironment is of clinically relevant significance in patients with axial osteosarcoma. Specifically, we identified both PD-L1+ TILs and CD8+ TILs as independent favorable prognostic markers.