• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.649-654
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• 2009

The immune system is comprised of cells and molecules whose collective and coordinated response to the introduction of foreign substance is referred to as the immune response. Defense against microbes is mediated by the early reaction (innate immunity) and the late response (adaptive immunity). Innate immunity consists of the epithelial barrier, phagocytes, complement and natural killer cells. Adaptive immunity, a more complex defense reaction, consists of activation of later-developed lymphocytes that, when stimulated by exposure to infectious agents, increase in magnitude and defensive capabilities with each successive exposure. In this review we discuss recent advances in important primary immune deficiency disorders of innate immunity (chronic granulomatous disease, leukocyte adhesion deficiency) and adaptive immunity (severe combined immune deficiency, Wiskott- Aldrich syndrome).

• Journal of Digestive Cancer Research
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• v.6 no.1
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• pp.11-15
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• 2018

Chemotherapy and surgical resection are the mainstay of cancer treatment. Particularly for chemotherapy, although it is effective method to care, sometimes cure various cancers, there are many different status of cancer not being controlled by chemotherapy such as recurrence and resistance to chemotherapy. In order to overcome those difficulties during cancer therapy, immunotherapy targeting immune cells and immune associated factors to enhance cancer immunity has been highlighted. Innate immunity plays important roles on initial stage of cancer immunity that are detecting, killing cancer cells and initiating adaptive immunity for cancer. So many basic and clinical studies to manage innate immunity for cancer therapy have been going on, and most of them were to stimulate innate immune cells including dendritic cell, macrophage, monocyte, and natural killer cell in various ways. They showed promising results but still there are many things to be resolved before clinical application. Herein, I review the role of innate immune cells and therapeutic trials for colorectal cancer.

• IMMUNE NETWORK
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• v.22 no.5
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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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• v.14 no.6
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• pp.265-276
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• 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.

• BMB Reports
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• v.51 no.5
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• pp.207-208
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• 2018

Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

• Molecules and Cells
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• v.20 no.2
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• pp.173-182
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• 2005

Heat shock protein gp96 is an endoplasmic reticulum chaperone, belonging to the HSP90 family. The function of gp96 as a molecular chaperone was discovered more than 10 years ago, but its importance has been overshadowed by the brilliance of its role in immune responses. It is now clear that gp96 is instrumental in the initiation of both the innate and adaptive immunity. Recently, the roles of gp96 in protein homeostasis, as well as in cell differentiation and development, are beginning to draw more attention due to rapid development in the structural study of HSP90 and some surprising new discoveries from genetic studies of gp96. In this review, we focus on the aspect of gp96 as an ER molecular chaperone in protein maturation, peptide binding and the regulation of its activity.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.45.1-45.16
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• 2020

IL-9 has been reported to play dual roles in the pathogenesis of autoimmune disorders and cancers. The collaboration of IL-9 with microenvironmental factors including the broader cytokine milieu and other cellular components may provide important keys to explain its conflicting effects in chronic conditions. In this review, we summarize recent findings on the cellular sources of, and immunological responders to IL-9, in order to interpret the role of IL-9 in the regulation of immune responses. This knowledge will provide new perspectives to improve clinical benefits and limit adverse effects of IL-9 when treating pathologic conditions.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• Journal of the korean veterinary medical association
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• v.48 no.3
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• pp.177-191
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• 2012

2011년도 Nobel 생리(生理) 의학상(醫學賞) : 자연(自然)(선천)(先天) 면역(免疫)(innate immunity)의 활성화에 관한 연구업적으로 B. A. Beutler와 J. A. Hoffmann, 그리고 수지상세포(樹枝狀細胞)(dendritic cell; DC)발견과 적응(適應)(획득)(獲得)면역(免疫)(adaptive immunity)에 있어서의 그들 세포의 역할을 밝혀낸 R. M. Steinman의 공동수상으로 금년도 Nobel 생리 의학상 수상자가 결정되었다는 보도가 지난 10월 3일 있었다(1-3). 그들의 업적을 요약하면 대략 다음과 같다. (Steinman교수는 Nobel수상자 발표 3일전인 9월 30일 암으로 사망함). 그들은 면역기구(immune system)의 활성화의 관건(key)이 되는 원리를 밝혀냄으로써, 면역기구에 관한 우리들의 이해를 혁신하였던 것이다. 과학자들은 오랫동안 세균(bacteria)이나 기타 미생물병원체들에 의한 공격에 대비하여 그들 자신을 방어하는 사람이나 기타 동물체에서의 면역응답(免疫應答)(immune response)의 문지기들을 탐색해 왔다. Beutler와 Hoffmann은 그와 같은 병원미생물을 인식하여 생체의 면역응답의 첫 단계인 자연면역을 활성화 할 수 있는 수용체 단백질(toll-like receptor protein)을 규명한 것이다(4,5). 한편 Steinmann은 면역계의 수지상세포(DC)와 병원미생물이 생체로부터 배제되는 면역응답의 후기단계인 적응면역을 활성화하고 조절하는 그들의 독특한 재능을 규명해 낸 것이다(6-8). 그들 3명의 발명은, 면역응답의 자연 및 적응 양상(樣相)이 어떻게 활성화되는 가를 밝혀냄으로써 질병의 기전에 관한 참신한 식견(識見)을 제공한 것이다. 그들의 연구는 감염병(感染病)(infectious disease), 암(癌)(cancer) 그리고 염증성질환(炎症性疾患)(inflammatory disease)에 대응하는 예방과 치료의 개발을 위한 새로운 방법을 개척한 것이다.

• Journal of Korean Traditional Oncology
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• v.10 no.1
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• pp.75-86
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• 2005

Disease associated with microorganisms are far from resolved by current therapeutics. One of effective approach to health maintenance and disease control is the use of dietary bacterial and carbohydrate supplements. This comprises use of probiotics and prebiotics. Probiotics mean the live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Prebiotics mean a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria that can Improve the host health. Especially, probiotics has the relation which is close with innate immunity and adaptive immunity. And probiotics has the clinical value with many disease like lactose intolerance, constipation, acute gastroenteritis, food hypersensitivity and allergy, atopic dermatitis, crohn's disease, rheumatoid arthritis, pelvic radiotherapy, intestinal inflammation and chemical exposure, colon cancer, inhibitory effect of Helicobacter pylori and lowering the level of cholesterol. We use jointly korean medicine and probiotics and it has the more therapeutic effect in the many disease.