• Molecules and Cells
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• v.46 no.10
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• pp.579-588
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• 2023

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.31.1-31.16
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• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.5.1-5.15
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• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• Korean Journal of Biological Psychiatry
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• v.22 no.2
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• pp.29-33
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• 2015

The brain maintains homeostasis and normal microenvironment through dynamic interactions of neurons and neuroglial cells to perform the proper information processing and normal cognitive functions. Recent post-mortem investigations and animal model studies demonstrated that the various brain areas such as cerebral cortex, hippocampus and amygdala have abnormalities in neuroglial numbers and functions in subjects with mental illnesses including schizophrenia, dementia and mood disorders like major depression and bipolar disorder. These findings highlight the putative role and involvement of neuroglial cells in mental disorders. Herein I discuss the physiological roles of neuroglial cells such as astrocytes, oligodendrocytes, and microglia in maintaining normal brain functions and their abnormalities in relation to mental disorders. Finally, all these findings could serve as a useful starting point for potential therapeutic concept and drug development to cure unnatural behaviors and abnormal cognitive functions observed in mental disorders.

• BMB Reports
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• v.48 no.6
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• pp.313-318
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• 2015

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix (ECM) and regulate the extracellular microenvironment. Despite the significant role that MMP activity plays in cell-cell and cell-ECM interactions, migration, and differentiation, analyses of MMPs in vitro and in vivo have relied upon their abundance using conventional immunoassays, rather than their enzymatic activities. To resolve this issue, diverse nanoprobes have emerged and proven useful as effective activity-based detection tools. Here, we review the recent advances in luminescent nanoprobes and their applications in in vitro diagnosis and in vivo imaging of MMP activity. Nanoprobes with the purpose of sensing MMP activity consist of recognition and detection units, which include MMP-specific substrates and luminescent (fluorescent or bioluminescent) nanoparticles, respectively. With further research into improvement of the optical performance, it is anticipated that luminescent nanoprobes will have great potential for the study of the functional roles of proteases in cancer biology and nanomedicine. [BMB Reports 2015; 48(6): 313-318]

• Proceedings of the KSME Conference
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• 2001.06d
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• pp.648-653
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• 2001

This study represents the numerical analysis of natural convection of a microenvironments with a air permeability in the clothing air-layer. The clothing air layer of shoulder and arm was used for numerical analysis model. As a numerical analysis method, we adopted a finite volume method for two-dimensional laminar flow, and analyzed the flow and thermal characteristics of velocity, temperature and concentration in the air layer between body and clothing. As a temperature boundary conditions, we considered that a body skin has a high temperature with $34^{\circ}C$ the environmental temperatures are $5,\;15\;and\;25^{\circ}C$ for various permeability coefficients. The distributions of concentration, temperature and velocity were showed that two large cells were. formed at horizontal and vertical air layer, respectively. As the temperature difference between body skin and environment decrease, the heat transfer was decreased rapidly.

• The Research Journal of the Costume Culture
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• v.6 no.4
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• pp.229-237
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• 1998

The ventilation efficiency of clothing was investigated by a trace gas method using a manikin wearing an impermeable overall under an isothermal condition, where the ventilation occurred only through the openings by diffusion. The ventilation patterns were different for each part of the body. The ventilation efficiency in the clothing microenvironment of the arm and the leg greatly depended on the distance from each opening when the wrist- or the ankle-opening was opened. When both side of wrist- or ankle-openings were opened to provide the opening area double respectively, the ventilation efficiency did not correspondingly increase twice, as compared one side opened. Even though it as certainly affected by the opening area, the ventilation efficiency was more significantly influenced by the position of openings.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.253-259
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• 2008

Human follicular fluid (HFF) is the in vivo microenvironment for oocyte maturation and includes a variety of proteins that could be involved in oocyte development and fertilization. We therefore used a proteomic approach to identify new HFF proteins. HFF from mature human follicles was obtained from five women following oocyte collection for in vitro fertilization (IVF). Ethanol-precipitated HFF run on two-dimensional gel electrophoresis (2DE) produced approximately 250 Coomassie brilliant blue-stained spots, 64 of which were identified using matrix-assisted laser desorption/ionization-mass spectrometry (MALDIMS). In this study, several proteins including complement factor H, inter-${\alpha}$ (globulin) inhibitor H4, inter-${\alpha}$-trypsin inhibitor heavy chain H4 precursor, human zinc-${\alpha}$-2-glycoprotein chain B, PRO2619, PRO02044, and complex-forming glycoprotein HC were new proteins that have not been previously reported in HFF using proteomic methods. Additionally, we identified alloalbumin venezia for the first time from trichloroacetic acid (TCA)-precipitated HFF. These HFF proteins could serve as new biomarkers for important human reproductive processes.

• Proceedings of the Materials Research Society of Korea Conference
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• 2011.10a
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• pp.2.2-2.2
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• 2011

The central strategy in tissue engineering involves a biomaterial scaffold as a delivery carrier of cells and a depot to deliver bioactive molecules. The ability of scaffolds to control cellular response to direct particular repair and regeneration processes is essential to obtain functional tissue engineering constructs. Therefore, many efforts have been made to understand local interactions of cells with their extracellular matrix (ECM) microenvironment and exploit these interactions for designing an ideal scaffold mimicking the chemical, physiological, and structural features of native ECM. ECM is composed of a number of biomacromolecules including proteins, glycosaminoglycans, and proteoglycans, which are assembled together to form complex 3-dimensional network. Electrospinning is a process to generate highly porous 3-dimensional fibrous structure with nano to micro scaled-diameter, which can closely mimic the structure of ECM. In this presentation, our approaches to develop biomimetic electrospun fibers for modulation of cell function will be discussed.

• BMB Reports
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• v.47 no.9
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• pp.483-487
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• 2014

Transmembrane 4 L six family member 5 (TM4SF5), as a membrane glycoprotein with 4 transmembrane domains, is similar to the tetraspanins in terms of membrane topology and plays important roles in tumorigenesis and tumor metastasis. Especially, TM4SF5 appears to form a massive protein-protein complex consisting of diverse membrane proteins and/or receptors in addition to cytosolic signaling molecules to regulate their signaling activities during the pathological processes. TM4SF5 is shown to interact with integrins ${\alpha}2$, ${\alpha}5$, and ${\beta}1$, EGFR, IL6R, CD151, focal adhesion kinase (FAK), and c-Src. This review focuses on the significance of the interactions with regards to TM4SF5-positive tumorigenesis and metastasis.