B7-H1 Expression in Malignant Pleural Mesothelioma is Associated with Sarcomatoid Histology and Poor Prognosis

Abstract

Introduction B7 homolog 1 [B7-H1; aka programmed cell death 1 ligand 1 (PD-L1)] is a negative costimulatory molecule that is associated with poor prognosis in many tumor types. Given the poor prognosis and the limited treatments available for mesothelioma, we decided to examine B7-H1 expression and its association with survival in patients with mesothelioma. Methods Expression of B7-H1 was determined in 106 patients using a mouse monoclonal anti-human B7-H1 (clone 5H1-A3) antibody with immunohistochemistry. Positive expression was defined as ≥5% positively-stained cells. Clinicopathologic features and survival were compared between B7-H1 positive and negative groups. Results Malignant mesotheliomas of 42 patients (40%) expressed B7-H1. Patients with B7-H1-postive tumors were less likely to be offered or undergo therapeutic surgery (p=0.03). All sarcomatoid mesotheliomas except one desmoplastic subtype expressed B7-H1. Survival was significantly decreased for patients whose tumors expressed B7-H1 (5 months median, 2-9.5 months interquartile range) compared to those whose tumors did not (14.5 months, 9.25-19 months; p<0.0001). In a multivariate model, B7-H1 expression and sarcomatoid mesothelioma remained significantly associated with worse survival [risk ratio 1.71, 95% CI 1.03-2.78 (p=0.04) and risk ratio 2.18, 1.08-4.23 (p=0.03) respectively]. Conclusions B7-H1 is expressed in a substantial proportion of malignant pleural mesotheliomas and is associated with poor survival. Almost all malignant pleural mesotheliomas with sarcomatoid differentiation expressed B7-H1. The expression of B7-H1 may have important therapeutic implications for the management of malignant pleural mesothelioma.

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

“…PD‐L1 appears to be expressed in a substantial proportion of human MPM 12, 24. Our IHC staining results also showed that 22.9% of human MPM had strong expression of PD‐L1, which indicate that some patients with MPM might benefit from anti‐PD‐1/PD‐L1 immunotherapy.…”

Novel systemic therapy against malignant pleural mesothelioma

“…MPM has a high variability of lymphocytic infiltration, but prolonged survival is associated with a higher presence of lymphoid cells (170). Additionally, PD-L1 expression is variable, is associated with populations of infiltrating T cells, and may be more associated with sarcomatoid histology and a worse prognosis (171)(172)(173)(174). Multiple clinical trials have sought to determine or are currently determining if MPM responds to immune mediated therapies ( Table 2).…”

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

“…Expression of programmed death-ligand 1 (PD-L1) on tumor cells and TILs has been described in literature. [6][7][8][9][10][11] However, only one series described PD-1 expression on tumor-infiltrating lymphocytes (TILs) 8 and nothing has been reported yet on TIM-3 and LAG-3 in human MPM tissue.…”