No abstract

Purpose Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. Experimental Design To characterize the immune microenvironment in HCC, IHC staining was performed for CD8-positive T lymphocytes, PD-1–positive, and LAG-3–positive lymphocytes, CD163-positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. Results Expression of CD8 was reduced in tumor, and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted. Conclusions LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC.

Long non-coding RNAs (lncRNAs) play key roles in various malignant tumors, including colorectal cancer (CRC). Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is overexpressed in CRC patients, but whether it affects CRC proliferation and metastasis via regulation of heat shock protein 27 (HSP27) remains unclear. In the present study, we found that DANCR was highly expressed and correlated with proliferation and metastasis in CRC. In addition, we demonstrated that DANCR and HSP27 were both targets of microRNA-577 (miR-577) and shared the same binding site. Furthermore, we revealed that DANCR promoted HSP27 expression and its mediation of proliferation/metastasis via miR-577 sponging. Finally, using an in vivo study, we confirmed that overexpression of DANCR promoted CRC tumor growth and liver metastasis. The present study demonstrated the function of DANCR in CRC and might provide a new target in the treatment of CRC.

MicroRNAs (miRNAs) are noncoding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b, and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma.