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Background Both iodine-125 implantation and transarterial chemoembolization (TACE) are feasible options for hepatocellular carcinoma (HCC). The aim of the research is to investigate whether iodine-125 implantation combined with TACE could improve the overall survival of patients with HCC of 3–5 cm. Methods 144 patients with HCC of 3–5 cm who underwent iodine-125 implantation plus TACE and TACE alone were retrospectively enrolled in this study. To reduce the selection bias, 55 matched pairs of patients were generated by propensity score matching (PSM). Their overall survival was compared by the Kaplan–Meier method. Independent prognostic factors were identified by Cox proportional hazards regression model. Results patients receiving iodine-125 implantation plus TACE have significantly better overall survival than patients receiving TACE alone ( P < 0.001). After PSM, treatment of iodine-125 plus TACE still provide better survival (1-year, 89.1% vs. 65.5%; 3-year, 51.0% vs. 7.4%; P < 0.001). In multivariate analysis, BCLC stage, vascular invasion and treatment modality independently predicted the prognosis. No severe adverse events occurred in both groups. Conclusion for HCC patients of 3–5 cm for whom surgical intervention is not an option, iodine-125 implantation combined with TACE might be an effective and viable alternative to provide better overall survival. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (pDCs) play immunosuppressive roles in the tumor microenvironment (TME). However, the molecular mechanisms underlying the recruitment and dysfunction of pDCs in the TME remain largely elusive, especially in hepatocellular carcinoma (HCC). In this study, we observed the accumulation of pDCs in the blood, tumor tissue, and ascitic fluid of HCC patients. A high density of tumor-infiltrating pDCs was correlated with poor prognosis in patients with HCC. Hypoxia-induced extracellular adenosine (eADO) significantly enhanced pDC recruitment into tumors via the adenosine A1 receptor (ADORA1). Mechanistically, hypoxia-inducible factor 1-alpha (HIF-1α) transcriptionally upregulated the expression of the ectonucleotidases CD39 and CD73 in HCC cells, both of which are essential for the generation of eADO. Moreover, eADO-stimulated pDCs promoted the induction of regulatory T cells and suppressed proliferation and cytotoxicity of CD8+ T cells. Depletion of pDCs using a monoclonal antibody or an ADORA1 antagonist significantly improved antitumor immunity and suppressed HCC growth in the immunocompetent HCC mouse model. Thus, targeting pDC recruitment may serve as a potential adjuvant strategy for immunotherapies in HCC. [ABSTRACT FROM AUTHOR]

Abstract: Although the ability of endogenous CD4−CD8− double negative (DN) T cells to suppress B cells has been documented, the extent to which ex vivo converted DN T cells suppress B cells activity is still being explored. The aim of this study was to determine whether and what extent ex vivo converted CD4−CD8− DN T cells suppress B cell activation and antibody production. We found that ex vivo converted DN T cells suppressed proliferation of activated B cells in a perforin and cell–cell contact dependent manner. In addition, ex vivo converted DN T cells significantly inhibited the production of IgG by stimulated B cells. This study provides evidence that ex vivo converted CD4−CD8− double negative T cells can down-regulate immune responses by suppressing B cell proliferation and IgG production, and supports efforts to develop ex vivo DN T cell therapies. [Copyright &y& Elsevier]

• Glypican-3 peptide functionalized on the surface of nanocarrier was synthesized and characterized. • The effective aqueous solubility of sorafenib was improved over 1900-fold. • in vivo uptake indicated great accumulation of targeted nanocarriers in tumor. • Tumor growth inhibition was observed by targeted nanocarrier therapy. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with increasing incidence. Chemotherapy is required for HCC patients after receiving surgical resection. Serious off-target induced side effects and systemic toxicity limit the clinical utility of drugs. Targeting therapeutic nanomedicine is an innovative strategy for enhancing drug delivery efficiency and reducing side effects. Here, we successfully formulated nanocarriers to encapsulate sorafenib, an FDA approved drug for treatment of HCC. Sorafenib is encapsulated with an entrapment efficiency >80% over 20 days. The effective aqueous solubility is improved over 1900-fold. The release ratio in vitro is characterized by a half-life of T 1/2 = 22.7 h. The peak target-to-background ratio for nanocarrier uptake by tumor occurs at 24 h post-injection, and is significantly greater for the target peptide versus controls. Ex vivo biodistribution confirms the in vivo results. Tumor regression is significantly greater for the target peptide versus controls after 21 days of therapy. No acute toxicity is found by blood chemistry or necropsy. In summary, a peptide specific for GPC3 has been identified, and used to modify the surface of a nanocarrier that encapsulates sorafenib with high entrapment efficiency. Regression of HCC xenograft tumors showed promise for targeted drug delivery. [ABSTRACT FROM AUTHOR]