• Title/Summary/Keyword: MDSC

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The emerging role of myeloid-derived suppressor cells in radiotherapy

  • Kang, Changhee;Jeong, Seong-Yun;Song, Si Yeol;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.38 no.1
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    • pp.1-10
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    • 2020
  • Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

Current Status of Heat Capacity Measurement Techniques for Ionic Liquids by DSC (DSC를 이용한 이온성 액체 열용량 측정 기술 현황)

  • Jo, Ye Lim;Kim, Ki-Sub;Park, Byung Heung
    • Journal of Institute of Convergence Technology
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    • v.4 no.1
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    • pp.5-8
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    • 2014
  • Recently ionic liquids received much attention as novel materials capable of replacing traditional solvents. The applicability of the ionic liquids should be determined based on their physico-chemical properties. Heat capacity is one of the most important properties to be considered when a process is developed using the ionic liquids and currently DSC has been proved as an effective technique to measure the heat capacity. Micro DSCII can measure heat capacities of various liquids by both an isothermal step method and a scanning method. DSC Q100 and MDSC are able to measure heat capacities of several ionic liquids. For each ionic liquid linear regression of the heat capacity as a function of temperature has been performed to increase accuracy. To investigate the feasibility of ionic liquids as PCMs, their heat capacities have been measured by using Pysis I DSC. This paper briefly summarizes the present techniques of measuring heat capacities of ionic liquids by DSC.

Mechanisms Underlying the Role of Myeloid-Derived Suppressor Cells in Clinical Diseases: Good or Bad

  • Yongtong Ge;Dalei Cheng;Qingzhi Jia;Huabao Xiong;Junfeng Zhang
    • IMMUNE NETWORK
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    • v.21 no.3
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    • pp.21.1-21.22
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    • 2021
  • Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes. Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Compatibility of biodegradable poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) blends for packaging application

  • Bhatia, Amita;Gupta, Rahul K.;Bhattacharya, Sati. N.;Choi, H.J.
    • Korea-Australia Rheology Journal
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    • v.19 no.3
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    • pp.125-131
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    • 2007
  • Biodegradable polymeric blends are expected to be widely used by industry due to their environmental friendliness and comparable mechanical and thermal properties. Poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) are such biodegradable polymers which aim to replace commodity polymers in future applications. Since cost and brittleness of PLA is quite high, it is not economically feasible to use it alone for day to day use as a packaging material without blending. In this study, blends of PLA and PBS with various compositions were prepared by using a laboratory-scale twin-screw extruder at $180^{\circ}C$. Morphological, thermal, rheological and mechanical properties were investigated on the samples obtained by compression molding to explore suitability of these compositions for packaging applications. Morphology of the blends was investigated by scanning electron microscopy (SEM). Morphology showed a clear phase difference trend depending on blend composition. Modulated differential scanning calorimetry (MDSC) thermograms of the blends indicated that the glass transition temperature ($T_g$) of PLA did not change much with the addition of PBS, but analysis showed that for PLA/PBS blend of up to 80/20 composition there is partial miscibility between the two polymers. The tensile strength and modulus were measured by the Instron Universal Testing Machine. Tensile strength, modulus and percentage (%) elongation at break of the blends decreased with PBS content. However, tensile strength and modulus values of PLA/PBS blend for up to 80/20 composition nearly follow the mixing rule. Rheological results also show miscibility between the two polymers for PBS composition less than 20% by weight. PBS reduced the brittleness of PLA, thus making it a contender to replace plastics for packaging applications. This work found a partial miscibility between PBS and PLA by investigating thermal, mechanical and morphological properties.

Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)

  • Nam, Sorim;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.63-70
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    • 2019
  • Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee;Lee, Byung-Hyun;Kim, Seong-Eun;Kwon, Bo-Eun;Jeong, Hyunjin;Choi, Jong Rip;Kim, Min Jung;Park, Yong;Kim, Byung Soo;Kim, Dae Hee;Ko, Hyun-Jeong
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.166-174
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    • 2021
  • Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.