• IMMUNE NETWORK
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• 제22권5호
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• pp.38.1-38.24
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• 2022

Exosomes, which are well-known nanoscale extracellular vesicles, are multifunctional biomaterials derived from endosomes and perform various functions. The exosome is a critical material in cell-cell communication. In addition, it regulates the pathophysiological conditions of the tumor microenvironment in particular. In the tumor microenvironment, exosomes play a controversial role in supporting or killing cancer by conveying biomaterials derived from parent cells. Innate immunity is a crucial component of the host defense mechanism, as it prevents foreign substances, such as viruses and other microbes and tumorigenesis from invading the body. Early in the tumorigenesis process, the innate immunity explicitly recognizes the tumor via Ags and educates the adaptive immunity to eliminate it. Recent studies have revealed that exosomes regulate immunity in the tumor microenvironment. Tumor-derived exosomes regulate immunity against tumor progression and metastasis. Furthermore, tumor-derived exosomes regulate polarization, differentiation, proliferation, and activation of innate immune cells. Exosomes produced from innate immune cells can inhibit or support tumor progression and metastasis via immune cell activation and direct cancer inhibition. In this study, we investigated current knowledge regarding the communication between tumor-derived exosomes and innate immune cell-derived exosomes (from macrophages, dendritic cells, NK cells, and neutrophils) in the tumor microenvironment. In addition, we discussed the potential development of exosomal immunotherapy using native or engineered exosomes against cancer.

• IMMUNE NETWORK
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• 제20권1호
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• pp.8.1-8.15
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• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• IMMUNE NETWORK
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• 제20권1호
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• pp.11.1-11.14
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• 2020

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

• IMMUNE NETWORK
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• 제12권5호
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• pp.165-175
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• 2012

Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen up-take into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants.

• IMMUNE NETWORK
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• 제5권4호
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• pp.232-236
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• 2005

Background: A physically active lifestyle and regular exercise training incurs many health benefits. One recently recognized benefit of regular moderate exercise is stress reduction and immune enhancement. Thus, a physical stress such as exercise may act at any number of points in the complex sequence of events collectively termed the immune response. Although exercise causes many propound changes in parameters of immune function, the nature and magnitude of such changes rely on several factors including the immune parameters of interest; type, intensity, and duration of exercise; fitness level or exercise history of the subject; environmental factors such as ambient temperature and humidity. Methods: This study was undertaken to investigate the effect of different type of exercise on superoxide dismutase (SOD), neutrophils, and T lymphocytes of Sprague-Dawley rats. Sprague-Dawley rats were randomly divided into three groups; a non-Trained group (NTG, n=6), a swim-Trained group (STG), and a treadmill-Trained group (TTG). The exercise regimen was designed in a treadmill (5 times/5 days/week) during 8-weeks for TTG, and swim training (5 times/5 days/week) during 8-weeks for STG, and the volume of exercise training was the same in both groups. Results: 8 weeks of regular swim and treadmill training significantly increased liver SOD concentration however, muscle SOD concentration was not statistically significant. In the level of neutrophils, TTG and STG showed significant difference, compared to NTG. TTG was the highest level of neutrophils. In the level of immune cell counts, there was significant difference among TTG, STG, and NTG both in the spleen and thymus. Conculsion: In conclusion, it can be stated that eight weeks swim and treadmill exercise training has beneficial effect in improving immune response and antioxidant defence capacity by augmenting immune cells and SOD activities of SD rats.

• IMMUNE NETWORK
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• 제24권3호
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• pp.21.1-21.16
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• 2024

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1β is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

• 한국지능시스템학회:학술대회논문집
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• 한국퍼지및지능시스템학회 2001년도 춘계학술대회 학술발표 논문집
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• pp.171-174
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• 2001

기존의 침입 탐지 시스템(Intrusion Detection System)은 점점 복잡해져 가는 네트워크, 다양화되고 지능화되는 해킹 기술과 바이러스의 공격으로부터 시스템을 보호하기 위해 처리해야 하는 정보의 양과 복잡한 알고리즘으로 인해 실시간 서비스의 구현이 힘들다는 문제점이 있다. 본 논문에서는 시스템, 네트워크 리소스의 효율적인 분배를 통해 실시간으로 침입자를 탐지할 수 있는 네트워크 토폴로지 즉, 디지털 면역 네트워크(Digital Immune Network, DIN)를 제시한다. DIN은 침입의 탐지를 위하여 생체 면역 시스템의 B세포, T세포 개념의 알고리즘이 적용되고, 견고성 향상을 위해 메쉬 네트워크 구조가 적용되어 호스트 연합(Host Alliance)을 구성함으로써 호스트들의 병렬처리를 통해 리소스 낭비를 막고 실시간 서비스가 제공될 수 있도록 하였다.

• IMMUNE NETWORK
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• 제9권1호
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• pp.1-3
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• 2009

• IMMUNE NETWORK
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• 제14권6호
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• IMMUNE NETWORK
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• 제15권2호
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.