Prognostic value of PD-L1 and PD-1 expression in pulmonary neuroendocrine tumors

Abstract

PurposeProgrammed death 1 (PD-1) receptor and its ligand, programmed death ligand-1 (PD-L1), play critical roles in the immune invasion of various tumors. This study aimed to explore the clinical significance of PD-L1/PD-1 expression in the progression of pulmonary neuroendocrine tumors (PNETs).MethodsThe expression of PD-L1 and PD-1 in 80 patients diagnosed with PNETs were investigated. Immunohistochemical analysis was performed on 80 formalin-fixed paraffin-embedded tissue specimens from PNETs and 20 corresponding cancer-adjacent tissue specimens.ResultsTissues from PNETs had higher levels of PD-L1 (58.8%) and PD-1 (51.3%) compared to the cancer-adjacent tissues (25% and 20%, respectively). Meanwhile, PD-L1 expression was associated with PD-1 expression (P=0.007). PD-L1 expression was significantly associated with histological type (P=0.014) and tumor stage (P=0.014). Univariate analyses showed that the overall survival time of PNETs patients was significantly associated with PD-L1 expression in cancer cells (P=0.003), PD-1 expression in tumor-infiltrating lymphocytes (P=0.001), tumor node metastasis stage (P<0.05), and distant metastasis (P<0.001). Additionally, multivariate analysis revealed that PD-L1 expression, PD1 expression, and distant metastasis of PNETs were independently associated with survival time. Moreover, Kaplan–Meier survival curves analysis revealed that patients with negative PD-L1 and PD-1 expression had better prognoses.ConclusionData suggested that PD-L1 and PD-1 can be useful prognostic biomarkers for survival and can pave the way toward new immunotherapy regimens against PNETs through targeting the PD-L1/PD-1 pathway.

Expression Patterns, Prognostic Value, and Intratumoral Heterogeneity of PD-L1 and PD-1 in Thymoma and Thymic Carcinoma

“…[36][37][38][39] Similarly, there are studies showing prognostic value of PD-L1 and PD-1 in pancreatic cancer, colon cancer, and pulmonary neuroendocrine cancer, among others. [40][41][42][43][44] The efficacy and safety of immunotherapy was evaluated in a recently published phase 2 trial of pembrolizumab in patients with thymic carcinoma, with a 22.5% response rate, including one complete response; however, autoimmune-related toxicities developed in several patients. 23 Although immunotherapy appears to be a promising treatment for patients with thymoma and thymic carcinoma, the risk of immune-related adverse events and the lack of response in the majority of patients show the necessity of investigating robust biomarkers predictive of response.…”

Hypoxia‐inducible factor‐1α and nuclear factor‐κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non‐small‐cell lung cancer cells

“…As important immune checkpoint molecules, PD‐1/PD‐L1 interaction suppresses the growth and function of effector T cells by inducing T cell apoptosis, anergy, and exhaustion and regulating the secretion of various cytokines . Tumor cells with PD‐L1 overexpression have been reported to be related to aggressive behavior and worse disease control and treatment outcomes …”

“…9,10 Tumor cells with PD-L1 overexpression have been reported to be related to aggressive behavior and worse disease control and treatment outcomes. [11][12][13] A growing amount of evidence has elucidated the intrinsic and extrinsic mechanisms of PD-L1 expression regulation in cancer cells. 14 Inflammatory cytokines, such as IFNγ, can induce PD-L1 expression through the MEK/ERK or JAK/STAT pathway.…”

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia

“…Furthermore, PD-1 and its ligands appear to be also expressed in well-differentiated intestinal and pancreatic NETs [23,24]. Conflicting results have been reported on PD-1 and PD-L1 as prognostic factors, since their expression was associated with worse overall survival in patients with pulmonary and metastatic GEP-NENs [18,25], whereas in lung NECs, both tumor-associated inflammation and PD-L1 positivity correlated with prolonged survival [7]. …”