Analysis of Expression of Programmed Cell Death Ligand 1 (PD-L1) and BRAF(V600E) Mutation in Thyroid Cancer

SIMPLE SUMMARY: Immune checkpoint inhibitors are expected to be used in clinical practice to treat thyroid cancer. Programmed cell death ligand 1 (PD-L1) is the ligand expressed on the surface of tumor cells. Recent studies have reported that PD-L1 overexpression can impede T cell activation and result in tumor growth. In thyroid cancer, it has been suggested that PD-L1 overexpression is associated with some clinicopathological factors and prognosis. However, the characteristics of the tumor microenvironment of thyroid cancer or expression of PD-L1 have not yet been clarified; the effectiveness of anti-PD-L1 antibody to thyroid cancer is unclear. We found that PD-L1 expression is associated with BRAF(V600E) mutation, CD8+ expression and low T cell activation, suggesting a mechanism of tumor evasion from the immune surveillance system in thyroid cancer. This new finding suggests that immune checkpoint inhibitors can be also expected to be effective in thyroid cancer. ABSTRACT: In thyroid cancer, it has been suggested that PD-L1 overexpression is associated with some clinicopathological factors and prognosis. The aim of this study is to characterize the expression of PD-L1, the presence of the BRAF(V600E) mutation, as well as cellular and humoral immunity in thyroid cancer, and to investigate the factors that predict the effectiveness of anti-PD-L1 antibody therapy. Blood samples were collected from 33 patients who were newly diagnosed with thyroid cancer after surgery or biopsy. PD-L1 expression, BRAF(V600E) mutation, and CD8+ expression were examined by immunohistological staining using clinical thyroid cancer specimens. With a PD-L1 staining cut-off value of 1%, 13 (39.4%) patients were classified as PD-L1 positive. Stimulation Index (SI) is an indicator of T cell activation. PD-L1 expression was significantly correlated with low SI level (p = 0.046). Moreover, BRAF(V600E) mutation was detected in 24 of the 33 (72.7%) patients, and was significantly associated with PD-L1 expression (p = 0.047). In addition, enhanced CD8+ expression was significantly associated with PD-L1 expression (p = 0.003). Multivariate analyses confirmed that high CRP levels (p = 0.039) were independently and significantly associated with poor progression-free survival. These findings suggest that elevated PD-L1 status can be a prognostic indicator for survival in patients with thyroid cancer when comprehensively assessed using the expression of CD8+, the presence of BRAF(V600E) mutation and the patient’s immune status.