• IMMUNE NETWORK
• /
• v.14 no.6
• /
• pp.265-276
• /
• 2014

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

• IMMUNE NETWORK
• /
• v.22 no.1
• /
• pp.2.1-2.22
• /
• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

• IMMUNE NETWORK
• /
• v.22 no.1
• /
• pp.10.1-10.17
• /
• 2022

Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

• IMMUNE NETWORK
• /
• v.4 no.2
• /
• pp.73-80
• /
• 2004

Viruses are obligate intracellular parasites which cause infection by invading and replicating within cells. The immune system has mechanisms which can attack the virus in extracellular and intracellular phase of life cycle, and which involve both non-specific and specific effectors. The survival of viruses depends on the survival of their hosts, and therefore the immune system and viruses have evolved together. Immune responses to viral infection may be variable depending on the site of infection, the mechanism of cell-to-cell spread of virus, physiology of the host, host genetic variation, and environmental condition. Viral infection of cells directly stimulates the production of interferons and they induce antiviral state in the surrounding cells. Complement system is also involved in the elimination of viruses and establishes the first line of defence with other non-specific immunity. During the course of viral infection, antibody is most effective at an early stage, especially before the virus enters its target cells. The virus- specific cytotoxic T lymphocytes are the principal effector cells in clearing established viral infections. But many viruses have resistant mechanism to host immune responses in every step of viral infection to cells. Some viruses have immune evasion mechanism and establish latency or persistency indefinitely. Furthermore antibodies to some viruses can enhance the disease by the second infection. Immune responses to viral infection are very different from those to bacterial infection.

• IMMUNE NETWORK
• /
• v.15 no.1
• /
• pp.16-26
• /
• 2015

The female reproductive tract has two main functions: protection against microbial challenge and maintenance of pregnancy to term. The upper reproductive tract comprises the fallopian tubes and the uterus, including the endocervix, and the lower tract consists of the ectocervix and the vagina. Immune cells residing in the reproductive tract play contradictory roles: they maintain immunity against vaginal pathogens in the lower tract and establish immune tolerance for sperm and an embryo/fetus in the upper tract. The immune system is significantly influenced by sex steroid hormones, although leukocytes in the reproductive tract lack receptors for estrogen and progesterone. The leukocytes in the reproductive tract are distributed in either an aggregated or a dispersed form in the epithelial layer, lamina propria, and stroma. Even though immune cells are differentially distributed in each organ of the reproductive tract, the predominant immune cells are T cells, macrophages/dendritic cells, natural killer (NK) cells, neutrophils, and mast cells. B cells are rare in the female reproductive tract. NK cells in the endometrium significantly expand in the late secretory phase and further increase their number during early pregnancy. It is evident that NK cells and regulatory T (Treg) cells are extremely important in decidual angiogenesis, trophoblast migration, and immune tolerance during pregnancy. Dysregulation of endometrial/decidual immune cells is strongly related to infertility, miscarriage, and other obstetric complications. Understanding the immune system of the female reproductive tract will significantly contribute to women's health and to success in pregnancy.

• IMMUNE NETWORK
• /
• v.9 no.4
• /
• pp.115-121
• /
• 2009

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of posttranscriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation.

• 제어로봇시스템학회:학술대회논문집
• /
• 2003.10a
• /
• pp.2372-2377
• /
• 2003

Nonlinear dynamic system exist widely in many types of systems such as chemical processes, biomedical processes, and the main steam temperature control system of the thermal power plant. Up to the present time, PID Controllers have been used to operate these systems. However, it is very difficult to achieve an optimal PID gain with no experience, because of the interaction between loops and gain of the PID controller has to be manually tuned by trial and error. This paper suggests control approaches by immune fuzzy for the nonlinear control system inverted pendulum, through computer simulation. This paper defines relationship state variables $x,{\dot{x}},{\theta},\dot{\theta}$ using immune fuzzy and applied its results to stability.

• 제어로봇시스템학회:학술대회논문집
• /
• 2003.10a
• /
• pp.1371-1376
• /
• 2003

In the thermal power plant, the main steam temperature is typically regulated by the fuel flow rate and the spray flow rate, and the reheater steam temperature is regulated by the gas recirculation flow rate. However, Strictly maintaining the steam temperature can be difficult due to heating value variation to the fuel source, time delay changes in the main steam temperature, the change of the dynamic characteristics in the reheater. Up to the present time, PID Controller has been used to operate this system. However, it is very difficult to achieve an optimal PID gain with no experience, since the gain of the PID controller has to be manually tuned by trial and error. This paper focuses on tuning of the 2-DOF PID Controller on the DCS for steam temperature control using immune based multiobjective approach. The stable range of a 2-DOF parameter for only this system could be found for the start-up procedure and this parameter could be used for the tuning problem. Therefore tuning technique of multiobjective based on immune network algorithms in this paper can be used effectively in tuning 2-DOF PID controllers.

• Proceedings of the Korean Institute of Intelligent Systems Conference
• /
• 2003.09a
• /
• pp.525-530
• /
• 2003

This paper focuses on design of nonlinear power plant controller using immune based multiobjective fuzzy approach. The thermal power plant is typically regulated by the fuel flow rate, the spray flow rate, and the gas recirculation flow rate. However, Strictly maintaining the steam temperature can be difficult due to heating value variation to the fuel source, time delay changes in the main steam temperature. the change of the dynamic characteristics in the steam-turbine system. Up to the present time, PID Controller has been used to operate this system. However, it is very difficult to achieve an optimal PID gain with no experience, since the gain of the PID controller has to be manually tuned by trial and error. These parameters tuned by multiobjective based on immune network algorithms could be used for the tuning of nonlinear power plant.

• IMMUNE NETWORK
• /
• v.14 no.1
• /
• pp.1-6
• /
• 2014

Epstein-Barr virus (EBV) is etiologically associated with a variety of diseases including lymphoproliferative diseases, lymphomas, carcinomas, and autoimmune diseases. Humans are the only natural host of EBV and limited species of new-world monkeys can be infected with the virus in experimental conditions. Small animal models of EBV infection, required for evaluation of novel therapies and vaccines for EBV-associated diseases, have not been available. Recently the development of severely immunodeficient mouse strains enabled production of humanized mice in which human immune system components are reconstituted and express their normal functions. Humanized mice can serve as infection models for human-specific viruses such as EBV that target cells of the immune system. This review summarizes recent studies by the author's group addressing reproduction of EBV infection and pathogenesis in humanized mice.