Search

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains a health challenge with increasing incidence worldwide. Radiofrequency ablation (RFA) is a potentially curative option for patients with early-stage HCC. However, the high rate of tumor recurrence limits long-term survival when the tumors are larger than 2 cm and undergoing insufficient RFA (iRFA). Notably, in situ tumor necrosis due to thermal ablation is assumed to be a source of antigens that induce antitumor immunity. Therefore, mounting studies and trials have attempted to provide a rational and effective therapeutic strategy combining RFA and immunotherapy to treat HCC. Nowadays, many controversies and challenges with this combined therapeutic strategy remain to be resolved, such as the indications for adjuvant immunotherapy along with RFA in early HCC, the sequence of the two treatments in advanced HCC, and the optimal timing of immunotherapy before or after RFA. In addition, individualized treatment strategies need to be perfected for patients with HCC. [ABSTRACT FROM AUTHOR]

Recently, the emerging role of circular RNAs (circRNAs) in tumor development and progression has been a topic of great interest. Nevertheless, the effects of hepatic stellate cell (HSC)-derived exosomes in hepatocellular carcinoma (HCC) remain unclear. Here, we aim to explore the potential effect of HSC exosome-derived circWDR25 on the aggressiveness of HCC. Firstly, a microarray analysis of circRNAs was performed to profile and identify the differentially expressed circRNAs derived from HSC exosomes activated by HCC cells. Subsequently, the roles of circWDR25 in HCC tumor growth and aggressiveness were confirmed through in vitro and in vivo functional experiments. Moreover, RNA pull-down, dual-luciferase reporter assays, and fluorescent in situ hybridization (FISH) were performed to determine interactions in the circWDR25-miR-4474-3p-ALOX15 loop. Immunohistochemical analysis was also performed on a microarray of HCC tissues and peritumoral tissues. We found that overexpressed peritumoral circWDR25 was associated with survival and recurrence in patients with HCC and promoted the progression of HCC cells both in vitro and in vivo. Mechanistically, both exogenous and HSC exosomal-derived circWDR25 regulated the expression of ALOX15 by sponging miR-4474-3p and ultimately inducing an epithelial-to-mesenchymal transition (EMT) in HCC cells. Moreover, exogenous and HSC exosomal-derived circWDR25 promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells. In conclusion, circWDR25 facilitated HCC cell proliferation and invasion via the circWDR25/miR-4474-3p/ALOX15 and EMT axes and it promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells, thus providing insights into the mechanism of tumor aggressiveness mediated by HSC-derived exosomal circWDR25. [ABSTRACT FROM AUTHOR]

Members of the genus Treron (Columbidae) are widely distributed in southern Asia and the Indo-Malayan Region but their relationships are poorly understood. Better knowledge of the systematic status of this genus may help studies of historical biogeography and taxonomy. The complete mitochondrial genome of T. curvirostra was characterized, a first for the genus. It is 17,414 base pairs in length, containing two rRNAs, 22 tRNAs, 13 protein coding genes (PCGs), and one D-loop with a primary structure that is similar to that found in most members of Columbidae. Most PCGs start with the common ATG codon but are terminated by different codons. The highest value of the Ka/Ks ratio within 13 PCGs was found in ATP8 with 0.1937, suggesting that PCGs of the mitochondrial genome tend to be conservative in Columbidae. Moreover, the phylogenetic relationships within Columbidae, which was based on sequences of 13 PCGs, showed that (T. curvirostra + Hemiphaga novaeseelandiae) were clustered in one clade, suggesting a potentially close relationship between Treron and Hemiphaga. However, the monophyly of the subfamilies of Columbidae recognized by the Interagency Taxonomic Information System could not be corroborated. Hence, the position of the genus Treron in the classification of Columbidae may have to be revised. [ABSTRACT FROM AUTHOR]