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Adaptive immunity is acquired when foreign substances enter the body. Interestingly, this immune system exists not only higher organisms but also many bacteria. The CRISPR-Cas systems are the bacterial adaptive immune systems against foreign DNA and RNA derived from phages or plasmids. Many bacteria can memorize the sequences of foreign DNA and RNA, and remove them by means of these systems. Structural and functional studies of these systems have dramatically progressed over the past few years. In particular, one of the CRISPR-Cas systems, Cas9, has received considerable attention as a highly efficient tool for genome editing. [ABSTRACT FROM AUTHOR]

In extremely rare cases, the metastatic lesions of renal cell carcinoma (RCC) spontaneously regress after removal of the primary disease, and thus RCC has been considered to be immunogenic. Thus far, several immunotherapies including cytokine therapy, peptide vaccine and recent immune checkpoints inhibitors have been employed to treat patients with metastatic RCC. In this review, the recent progress in immunotherapy against RCC is surveyed and its future perspective is discussed. Our experimental research on galectin 9 and PINCH as promising immunotherapy targets is also mentioned.

Half a century has passed since Epstein-Barr virus (EBV) particles were isolated from the cultured lymphoblasts of Burkitt lymphoma. During the period, molecular biology, hematology/immunology, and transplantation medicine made amazing progress, that clarified the mode of infection and pathophysiology of the virus in human diseases. Research strategies on the relationship between EBV and human have expanded to the epidemiology, structures and functions of both genomes, regulatory genes including microRNA, and the nature of epigenetics. Although no animal models of EBV infection long hampered the completion of in vivo experiments, humanized mice have broken through a barrier of in vitro study on EBV-infected cell lines. Our understanding of the life cycle of EBV has continued to deepen about the infection via the CD21 receptor expressed on B cells, the latency, reactivation/reinfection, and transformation, and also the dynamics of T-cell immune response and the intracellular immunosurveillance beyond acquired and innate immunity. On the other hand, the disease entity of life-threatening lymphoproliferative disease of EBV-infected T cells or NK cells is on controversial. The other parts of this special issue include the recent topics of the basic and clinical researches of EBV as the oncogenic virus. Then, we herewith overview the research history of EBV with special reference to the infected cells and host immune responses in EBV-associated diseases.

Recently, autoimmune pancreatitis (AIP) has been classified into two subtypes: type 1 as a pancreatic manifestation of IgG4-related disease (IgG4-RD), and type 2 related with a granulocytic epithelial lesion (GEL). Different from type 2 AIP, T helper type 2 (Th2) immune response is predominant over Th1 in type 1/IgG4-RD. Recent human and experimental animal studies have suggested a possible involvement of innate immunity in addition to acquired immunity, such as genetic background, bacterial/viral infections, complement activation via classical pathway, or IgG4-production of monocytes/basophils with TLR/NOD stimulation. Based on these findings, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-RD.

The recent vigorous transnational migration of people and materials reflecting the development of transportation facilities, changes in social structure, and war disasters has increased the global spread of emerging and re-emerging infectious diseases. Vaccine, which is the major fundamental prophylaxis against infectious diseases, has greatly contributed to the maintenance and improvement of human health worldwide. However, the disadvantages of conventional injection systems hamper the speedy mass-vaccination and the global distribution of vaccines. Transcutaneous immunization systems, which are easy-to-use and low-invasive methods of vaccination, have the potential to overcome certain issues associated with injectable vaccinations. In this review, we provide an outline of recent trends in the development of techniques for the transcutaneous delivery of vaccine antigens. We also introduce basic and clinical research involving our transcutaneous immunization systems that incorporate self-dissolving microneedle patch.

Human norovirus is a mutatable non-enveloped RNA virus capable of causing acute gastroenteritis in humans. Thus far, no experimental systems can propagate this virus in large amounts. Recent progresses in viral genomics and bioinformatics have led to a better understanding of molecular evolution of this virus in human populations. In addition, progresses in studies of the related noroviruses, those are replicable in laboratory systems, have led to a rapid accumulation of information on structural biology of norovirus. Furthermore, progresses in public health and water environment researches have led to a better understanding of viral ecology. In this review, I will first summarize fundamental characteristics of norovirus and its molecules. Then, I will summarize structure and molecular evolution of norovirus GII/4 subtype, which is now responsible for majorities of norovirus outbreaks in the world. Finally I will discuss survival strategies of human norovirus in nature by integrating the information.

The clinical outcome of intra-hepatic cholangiocelluler carcinoma (ICC) is very poor. To prevent a tumor relapse after curative operation, we employed the combination therapy of adaptive transfer of anti-CD3 activated T cells and dendritic cell vaccine therapy (DC-CAT therapy) since 2000. During DC-CAT therapy, about a half of patient revealed skin reaction positive. Moreover, the patient who had a skin reaction showed a significantly good clinical outcome. In this study, we investigated the difference between skin reaction positive and negative checking with the surface markers of T cells. The patient who had skin reaction positive increased the number of lymphocyte. Especially, CD8 positive T cells were increased about 2 folds in number before the DC-CAT therapy, and decreased Foxp3 positive regulatory T cells. Our data suggest that increasing cytotoxic T cells and decreasing regulatory T cells made the difference of the clinical outcome such as a disease free survival rate and overall survival rate after curative operation for ICC patient.