Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

BACKGROUND: The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer. METHODS: One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared. RESULTS: The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type. CONCLUSIONS The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.
B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms/drug therapy* ; Male