Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis.Though treatment modalities are available,mortality from this cancer remains high.Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival.Immunotherapy,with modern pharmacologic developments,is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation.This review will discuss current concepts of immunobiology in hepatocarcinogenesis along with current treatment modalities employing immunotherapy.The tumor microenvironment along with a variety of immune cells coexists and interplays to lead to tumorigenesis.Tumor infiltrating lymphocytes including CD8+ T cells,CD4+ T cells along with regulatory T cells,tumor associated macrophages,tumor associated neutrophils,myeloid derived suppressor cells,and natural killer cells interact to actively provide anti-tumor or pro-tumor effects.Furthermore,oncogenic pathways such as Raf/mitogenactivated protein kinase/extracellular-signal-regulated kinase pathway,phosphatidyl-3-kinase/AKT/mammalian target or rapamycin,Wnt/β-catenin,nuclear factor-κB and signal transducers and activators of transcription 3 may lead to activation and proliferation of tumor cells and are also considered cornerstones in tumorigenesis.Immunotherapy directed at this complex milieu of cells has been showned to be successful in cancer treatment.The use of vaccines,adoptive cell therapy and immune checkpoint inhibitor modulation are current options for therapy.Further translational research will shed light to concepts such as anti-tumor immunity which can add another alternative in the therapeutic armamentarium.

Immunobiology and immunotherapy of gestational trophoblastic disease

Gestational trophoblastic diseases are a heterogeneous group of pregnancy related tumors that show extensive metastatic spread but are readily responsive to chemotherapy.This one of a kind treatability of gestational trophoblastic tumors may to some extent be inferable from a host immunologic reaction to the paternal antigens that are expressed on the trophoblastic cells.In this review,we evaluate the current cognizance of immunobiology of gestational trophoblastic diseases and also establish the immunologic behaviour of gestational trophoblastic diseases which should be researched further in order to gain a better understanding of the aetiology of these neoplasias.This will further help structuring immunotherapeutic methodologies for their treatment.

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

BACKGROUND： Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES： The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS： The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species （ROS） and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly（I：C） induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis （HBV, HCV）, drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS： The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.

Recent advances of microneedles for biomedical applications: drug delivery and beyond

The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing(3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.