No abstract

Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.

BRAF(V600E) was not limited to LCH and was detected more frequently in histiocytic sarcoma. Our findings suggest that the BRAF pathway may contribute to the pathogenesis or malignant transformation of histiocytic and dendritic cell neoplasms.

Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1 + and CD8 + tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (Po 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (Po0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P = 0.054) and expression of EGFR and MET (Po 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (Po 0.001) and ERBB2 (P = 0.013). The numbers of CD8 + and programmed cell death-1 + lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (Po 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1 + /CD8 + lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

We found a significant correlation between the size of the solid component on thin-section CT and the invasive component on pathology.

PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.

No abstract

Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 -translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 (PD-L1) and H2228 (PD-L1) cells were transfected with or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression. PD-L1 expression was detected in 81% of-translocated pADCs; this value was significantly higher than those of pADCs with mutation, mutation or lacking or mutation ( <0.005 for all). Moreover, -translocated pADC with PD-L1 expression showed significantly higher numbers of tumor-infiltrating PD-1 cells. ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression. Transfection of H23 cells with enhanced PD-L1 expression, which was compromised by crizotinib treatment. This ALK-dependent upregulation of PD-L1 expression was mediated by STAT3 and hypoxia-inducible factor (HIF)-1α under normoxia and hypoxia. Furthermore, EML4-ALK enhanced HIF-1α expression through increasing transcription and decreasing ubiquitination of HIF-1α. In-translocated pADC tissues, significant positive correlations between PD-L1 and nuclear HIF-1α ( < 0.05) or pSTAT3 expression levels (<0.005) were observed. Among patients with -translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free ( = 0.001) and overall survival ( = 0.002) after crizotinib treatment. Collectively, our findings demonstrate that derived pADCs increase PD-L1 expression via HIF-1α and/or STAT3, thus providing a rationale for PD-1/PD-L1 pathway-targeted therapy in-translocated lung cancer.