ABSTRACT
The immune checkpoint molecule lymphocyte activation gene 3 (LAG-3) is currently being investigated as a possible target for immunotherapy in triple-negative breast cancer (TNBC), frequently as an addition to treatment with programmed cell death protein 1/programmed death ligand 1 (PD-L1) inhibition. However, expression of LAG-3, the frequency of coexpression with PD-L1, and the prognostic significance of this marker have not been studied extensively in TNBC. For this study, tissue microarrays (TMAs) were constructed from surgical specimens of 514 patients with TNBC. TMAs were stained immunohistochemically for LAG-3 and PD-L1 expression. Tumor-infiltrating lymphocytes (TILs) were evaluated on full glass slides. LAG-3 expression was significantly associated with improved overall survival and relapse-free survival. When adjusted for clinicopathologic factors, each increment of 10 LAG-3-positive intratumoral lymphocytes per TMA core was associated with improved overall survival (hazard ratio=0.93, 95% confidence interval: 0.89-0.97, P=0.002), and recurrence-free survival (hazard ratio=0.91, 95% confidence interval: 0.85-0.97, P=0.002). PD-L1 expression on immune cells and PD-L1 expression evaluated with the combined positive score and TILs were also associated with improved survival in both univariate and multivariate analyses. PD-L1 expression on tumor cells was only associated with improved survival in univariate analysis. LAG-3 expression was associated with both TILs and PD-L1 expression. Coexpression of LAG-3 and PD-L1 did not confer additional survival benefits. In conclusion, LAG-3 expression is associated with improved survival in TNBC. LAG-3 is often coexpressed with PD-L1, confirming that TNBC is likely a suitable candidate for cotreatment with LAG-3 and programmed cell death protein 1/PD-L1 inhibitors. However, coexpression does not confer additional survival benefits.
Subject(s)
Antigens, CD/genetics , Triple Negative Breast Neoplasms , B7-H1 Antigen/metabolism , Humans , Immunotherapy , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasm Recurrence, Local/metabolism , Prognosis , Triple Negative Breast Neoplasms/genetics , Lymphocyte Activation Gene 3 ProteinABSTRACT
During childhood two women developed yellowish xanthoma-like papules on the neck. After dermatological examination and skin biopsy, the diagnosis pseudoxanthoma elasticum (PXE) was made. PXE is a hereditary metabolic disease which has an early onset with characteristic skin lesions. Early diagnosis and follow-up is essential to prevent serious ocular or cardiovascular complications. Follow-up standards are lacking for these patients.
