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Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8^(+)T cell responses

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Cellular & Molecular Immunology 2021年第8期18卷 1956-1968页

作者： seon-Hee Kim Rohit singh Chungyong Han Eunjung Cho Yu I.Kim Don G.Lee Young H.Kim sang soo Kim Dong Hoon shin Hye Jin You Hyeon-Woo Lee byoung s.kwon Beom K.Choi Division of Tumor Immunology National Cancer CenterGoyang10408Republic of Korea Graduate school of Cancer science and Policy National Cancer CenterGoyang10408Republic of Korea Biomedicine Production Branch Program for Immunotherapy ResearchGoyang10408Republic of Korea Eutilex Institute for Biomedical Research EutilexCo.Ltd.Seoul08594Republic of Korea Division of Convergence Technology National Cancer CenterGoyang10408Republic of Korea Division of Translational science National Cancer CenterGoyang10408Republic of Korea Institute of Oral Biology School of DentistryGraduate SchoolKyung Hee UniversitySeoul02447Republic of Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA70112USA

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor ***,the adverse side effects associated with agonist antibodies have hindered their clinical ***,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB *** show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB ***,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γ*** was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T *** data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.

关键词： 4-1BB Costimulation Granuloma CD8 lymphocyte Macrophage

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4-1BB-4-1BBL cis-interaction contributes to the survival of selfreactive CD8^(+)T cell

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Cellular & Molecular Immunology 2023年第9期20卷 1077-1080页

作者： Eunjung Cho Rohit singh Chungyong Han seon-Hee Kim Kwang H.Kim Bo-Mi Park Dong Hoon shin seongeun Han Young H.Kim byoung s.kwon Ki Taek Nam Beom K.Choi Immuno-oncology Branch Division of Rare and Refractory CancerNational Cancer CenterGoyang 10408Republic of Korea severance Biomedical science Institute Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea Department of Cancer Biomedical science Graduate School of Cancer Science and PolicyNational Cancer CenterGoyang 10408Republic of Korea Department of Biomedical Laboratory science Catholic Kwandong UniversityGangneung 25601Republic of Korea Biomedicine Production Branch Research InstituteNational Cancer CenterGoyang 10408Republic of Korea Anticancer Resistance Branch Division of Rare and Refractory CancerResearch InstituteNational Cancer CenterGoyang 10408Republic of Korea Eutilex Co. Ltd.Geumcheon-guSeoul 08594Republic of Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA 70112USA Innobationbio Co. Ltd.Mapo-guSeoul 03929Republic of Korea

4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of... 详细信息

关键词： interaction activation knowledge

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Low cycle fatigue properties and cyclic deformation behavior of as-extruded AZ31 magnesium alloy

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Transactions of Nonferrous Metals society of China 2010年第B07期20卷 533-539页

作者： s.kwon K.sONG K.s.sHIN s.I.KWUN Department of Materials science and Engineering Korea University school of Materials science and Engineering Seoul National University

The low cycle fatigue(LCF)properties of as-extruded AZ31 Mg alloy were investigated under total strain amplitudes in the range of 0.4%-1.2%with strain rate of 1×10- 2s -*** to the twinning effect in compression during loading and the detwinning effect during unloading,the alloy showed an asymmetric hysteresis *** cyclic stress response exhibited cyclic hardening at high total strain *** cyclic deformation behaviors were discussed using the Coffin-Manson plot,which divided the plastic strain amplitudes into the tension side and the compression *** the LCF tests that were started from either tension or compression under a total strain amplitude of 1.0%,the interaction between the twinning effect and dislocation was *** twinning effect during the LCF test and the variation of the dislocation density were investigated using optical microscopy and transmission electron microscopy,respectively.

关键词： AZ31 magnesium alloy low cycle fatigue twinning dislocation

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Can an 8^(th) grade student learn point of care ultrasound?

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World Journal of Emergency Medicine 2019年第2期10卷 109-113页

作者： Alexander s.kwon shadi Lahham John C.Fox sage Hill school Department of Emergency Medicine UC Irvine Medical Center UC Irvine School of Medicine

BACKGROUND: Point-of-care ultrasound has gained widespread use in developing countries due to decreased cost and improved telemedicine capabilities. Ultrasound training, specifi cally image acquisition skills, is occurring with more frequency in non-medical personnel with varying educational levels in these underdeveloped areas. This study evaluates if students without a high school education can be trained to acquire useful FAsT images, and to determine if an 8^(th) grade student can teach peers these ***: The 8^(th) grade students at a small middle school were divided into two groups. One group received training by a certified medical sonographer, while the other group received training by a peer 8^(th) grade student trainer who had previously received training by the sonographer. After training, each student was independently tested by scanning the four FAsT locations. A blinded ultrasound expert evaluated these images and deemed each image adequate or inadequate for clinical ***: Eighty video image clips were obtained. The overall image adequacy rate was 74%. The splenorenal window had the highest rate at 95%, followed by retrovesical at 90%, hepatorenal at 75%, and subxiphoid cardiac at 35%. The adequacy rate of the sonographer-trained group was 78%, while the adequacy rate of the student-trained group was 70%. The difference in image adequacy rate between the two groups was not signifi cant(P-value 0.459).CONCLUsION: The majority of 8^(th) graders obtained clinically adequate FAsT images after minimal training. Additionally, the student-trained group performed as well as the sonographer-trained group.

关键词： Point of care ultrasound FAsT Image acquisition Training

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4-1BB signaling beyond T cells

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Cellular & Molecular Immunology 2011年第4期8卷 281-284页

作者： Dass s Vinay byoung s.kwon section of Clinical Immunology Allergyand RheumatologyDepartment of MedicineTulane University Health Sciences CenterNew OrleansLAUSA Cell and Immunobiology and R&D Center for Cancer TherapeuticsNational Cancer CenterIlsanGyeonggi-DoKorea

Originally discovered as a T cell-activating molecule,4-1BB(CD137)is now also recognized as an activator of non-T cells,thus imparting a new dimension to its potential in vivo effects.4-1BB expression is seen on a variety of non-T cells including activated dendritic cells(DCs),monocytes,neutrophils,B cells and natural killer(NK)cells,and promotes their individual effector *** T cell-and non-T cell-activating ability of 4-1BB may be the basis of its powerful anti-cancer,anti-autoimmune and anti-viral *** we discuss the consequence and importance of 4-1BB signaling in non-T *** consider its effects on immune regulation,and the distinct and/or overlapping pathways involved in these responses,as well as possible therapeutic applications.

关键词： APC cytokines natural killer cells T cells 4-1BB

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4-1BB signaling activates glucose and fatty acid metabolism to enhance CD8^(+) T cell proliferation

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Cellular & Molecular Immunology 2017年第9期14卷 748-757页

作者： Beom K Choi Do Y Lee Don G Lee Young H Kim seon-Hee Kim Ho s Oh Chungyong Han byoung s.kwon Cancer Immunology Branch Division of Cancer BiologyNational Cancer CenterGoyangGyeonggi 10408Korea Department of Internal Medicine Yonsei University College of MedicineSeoul 120-752Korea Immune Cell Production Unit Program for Immunotherapeutic ResearchNational Cancer CenterGyeonggi 10408Korea Eutilex Catholic University School of MedicineSeoul 06591Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA 70112USA

4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T *** these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid *** found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and *** with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid ***-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty *** also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB *** increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,*** conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.

关键词： AMPK CD8^(+)T cells 4-1BB(CD137) LKB1 metabolism

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An Efficient Organic Additive to Control the Crystallization Rate of Aliphatic Polyketone: A Non-isothermal Crystallization Kinetics study

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Chinese Journal of Polymer science 2017年第4期35卷 547-557页

作者： He-xin Zhang Min-Jeong Park Young-kwon Moon Eun-Bin Ko Xue-quan Zhang Keun-byoung Yoon Department of Polymer science and Engineering Kyungpook National University Key Laboratory of synthetic Rubber Changchun Institute of Applied ChemistryChinese Academy of Sciences

Three types of organic compounds--two carboxylic acids and an anhydride, were used as additives for polyketone （PK）. The effect of the additive structure and their feed ratios on the melting temperature, crystallization temperature, and crystallization rate of PK were studied. We found that the crystallization temperature could be reduced significantly by introducing a small quantity of organic additive, in particular, an anhydride. On addition of 1 phr of anhydride, the crystallization temperature was reduced by 10.7 ℃. Therefore, the non-isothermal crystallization kinetics of aliphatic PKJanhydride blends with various feed ratios was investigated using DsC. The results were analyzed by various theoretical models, such as Avrami, Ozawa and combined Avrami-Ozawa models.

关键词： Polyketone Anhydride Non-isothermal Crystallization kinetics

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New results on stability criteria for neural networks with time-varying delays

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Chinese Physics B 2011年第5期20卷 163-173页

作者： O.M.kwon J.W.kwon s.H.Kim school of Electrical Engineering Chungbuk National University410 SungBong-RoHeungduk-guCheongju 361-763Republic of Korea Department of Computer Engineering Kyungwon UniversitySan 65Sujung-guSungnam 461-701Republic of Korea school of Integrated Technology College of EngineeringYonsei University50 Yonsei-RoSeodaemun-guSeoul 120-749Republic of Korea

In this paper, the problem of stability analysis for neural networks with time-varying delays is considered. By constructing a new augmented Lyapunov-Krasovskii＇s functional and some novel analysis techniques, improved delaydependent criteria for checking the stability of the neural networks are established. The proposed criteria are presented in terms of linear matrix inequalities （LMIs） which can be easily solved and checked by various convex optimization algorithms. Two numerical examples are included to show the superiority of our results.

关键词： neural networks time-varying delays stability Lyapunov method

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CHARACTERIsTICs OF AN EXCAVATION DAMAGED ZONE DEVELOPED AROUND KAERI UNDERGROUND REsEARCH TUNNEL Paper No.194

CHARACTERISTICS OF AN EXCAVATION DAMAGED ZONE DEVELOPED AROU...

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IsRM-sponsored International symposium on Rock Mechanics:"Rock Characterisation,Modelling and Engineering Design Methods"(sINOROCK2009)

作者： s.kwon J.s.Kim W.J.Cho Korea Atomic Energy Research Institute

ISBN: (纸本)9789628014170

In Korea,a Korean reference disposal system(KRs) was developed for the permanent disposal of spent fuels in a deep geological *** order to validate the feasibility,safety,stability,and reliability of this system,an underground research tunnel, KAERI Underground Research Tunnel(KURT),was constructed as in *** is located in a mountain at the rear of the KAERI *** major rock type at the KURT site is granite,which is considered as one of the host rocks for a geological *** blasting was applied to reduce the outbreak and damaged *** diameters of the main blastholes and perimeter holes were 36mm and 17mm,*** advance rate was changed from 1.7 to 3.6m depending on the rock condition in the EDZ study *** characteristics of an EDZ around a tunnel were investigated with various laboratory as well as in situ *** this study,the influence of an EDZ on the mechanical,hydraulic,and thermal behaviors around the KURT and the conceptual repository design adapting the KRs was investigated based on three-dimensional computer simulations and the rock properties measured from the laboratory and in situ tests. (1) In situ test:A Goodman jack test showed that the deformation modules were influenced by a blasting to a depth of 0.6～2m. According to the RQDs of the rock cores from the EDZ study area,the average RQD in the 0～2m range,where the blasting impact is significant,was 67,while it was 81 at a deeper *** means the RQD was decreased by about 17%by the blasting. (2) Empirical equations:Empirical equations based on ground vibration predicted the EDZ as 0.3～2.3m. (3) Laboratory tests:From the laboratory tests,the EDZ size could be estimated to be around 0.9～*** elastic modules in the EDZ were decreased by about 56%.From a borehole radar reflection survey and a subtracting technique,it was possible to detect the new reflectors generated by a tunnel blasting. (4) Computer modeling:The influence of EDZ on mechanical

关键词： EDZ underground research tunnel MH coupling KURT blasting damage

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Restoration of an Inner-City stream and Its Impact on Air Temperature and Humidity Based on Long-Term Monitoring Data

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Advances in Atmospheric sciences 2009年第2期26卷 283-292页

作者： Kyu Rang KIM Tae Heon kwon Yeon-Hee KIM Hae-Jung KOO byoung-Cheol CHOI Chee-Young CHOI Applied Meteorology Research Laboratory National Institute of Meteorological Research Korea Meteorological Administration Applied Meteorology Research Laboratory National Institute of Meteorological ResearchKorea Meteorological Administration

spatiotemporal changes in air temperature and humidity associated with the restoration of an innercity stream in seoul, Korea, are investigated based on long-term monitoring data. The Cheonggye stream, covered under a concrete structure for 46 years, was restored in 2005 and runs 5.8 km eastward through a central region of seoul. Long-term monitoring of the air temperature and relative humidity was made along the stream throughout the restoration and across the stream after the restoration. The area along the stream had a higher air temperature than the entire metropolitan area. The temperature anomaly between the monitoring area and the surrounding metropolitan area was 0.13℃ lower on average at the center of the stream after the restoration. The stream＇s effect on the air temperature was also evident in the temperature distribution along a street traversing the stream. The relative and specific humidities were increased due to the restoration. The restored stream modified the nearby urban climate in the opposite direction compared to urbanization. The results could be used as a model case in mitigating urban climate by a stream in future urban planning practices.

关键词： urban heat island stream restoration land-use vegetation Cheonggye stream

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