• Journal of Chest Surgery
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• 제53권4호
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• pp.168-171
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• 2020

Adjuvant therapy for completely resected esophageal squamous cell carcinoma is less commonly applied in clinical practice than neoadjuvant therapy, but it plays a substantial role in improving survival for esophageal cancer patients. This article presents a concise review of the evidence regarding adjuvant therapy for esophageal squamous cell carcinoma and future directions, particularly immunotherapy.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.167-174
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• 2023

Development of hepatocellular carcinoma (HCC) is driven by a multistep and long-term process. Because current therapeutic strategies are limited for HCC patients, there are increasing demands for understanding of immunotherapy, which has made technological and conceptual innovations in the treatment of cancer. Here, I discuss HCC immunotherapy in the view of interaction between liver resident cells and immune cells.

• IMMUNE NETWORK
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• 제23권4호
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• 생명과학회지
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• 제19권7호
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• pp.886-891
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• 2009

Cancer/testis(CT) antigens은 여러 종료의 암에서는 발현이 되지만, 정상조직에서는 고환에서만 발현이 되는 특이성을 가지고 있다. 이러한 특이성은 immunotherapy을 하기 위한 항암백신 개발에 매력적인 유전자로 알려져 있다. 본 연구에서는 29개의 한국유방암조직에서 13개의 CT antigens (NY-SAR35, SCP-1, SSX-1, SSX-2, SSX-4, MAGE-1, MAGE-3, MAGE-4, MAGE-10, CT-7, NY-TLU57, NY-ESO-1, and LAGE-1)의 발현빈도를 RT-PCR을 통하여 조사하고 환자의 임상학적 분류와 CT antigens의 발현빈도에 대하여 조사하였다. 29개의 유방암조직에 RT-PCR결과, 13개의 CT antigen중에 MAGE-3 (66%)와 MAGE-1(57%)에서 발현빈도가 가장 높았고 LAGE-1 (55%),NY-SAR-35 (49%),MAGE-4(41%), NY-ESO-1(38%), CT-7(24%), SSX-4(24%)순으로 발현빈도를 보였다. 그러나 SSX-1, SSX-2. MAGE-10와 NY-TLU-57의 발현은 3-7%로 매우 낮았고 특히 SCP-1는 발현되지 않았다. 29 유방암 조직에서 적어도 하나 이상의 CT antigen이 발현되는 샘플은 28(98%)이였다. 그러나 환자의 임상학적 분류와 CT antigens의 발현빈도와는 특징적인 관꼐가 없음을 알수있었다. 29개의 유방암조직에서 MAGE-3와 NY-ESO-1의 Protein level에서의 발현을 알아보기 위하여monoclonal antibody를 이용하여 면역조직염색을 하였다. MAGE-3은 29개 조직중에서 12개의 조직에서 발현되었으며 NY-ESO-1은 11개의 조직에서 발현되었다. 그러므로 CT antigens은 한국 유방암 조직에서 빈번하게 발현된 것을 알 수 있었으며 CT antigens을 기반으로 한 암 백신개발의 잠재적인 표적이 될 수 있을 것이라 사료된다.

• Radiation Oncology Journal
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• 제38권1호
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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.

• 대한의생명과학회지
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• 제25권4호
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• pp.398-406
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• 2019

Cancer immunotherapy using gene-modified tumor cells is safe and customized cancer treatment method. In this study, we made gene-modified tumor cells by transferring costimulatory molecules, 4-1BBL and OX40L, into tumor cells using lentivirus vector, and identified anti-cancer effect of gene-modified tumor cells in CT26 mouse colorectal tumor model. We construct pLVX-puro-4-1BBL, -OX40L vector for lentivirus production and optimized the transfection efficiency and transduction efficiency. The transfection efficiency is maximal at DNA:cationic polymer = 1:0.5 and DNA 2 ㎍ for lentivirus production. Then, the lentiviral including 4-1BBL and OX40L was used to deliver CT26 mouse tumor cells to establish optimal delivery conditions according to the amount of virus. The transduction efficiency is maximal at 500 μL volume of lentiviral stock without change in cell shape or growth rate. CT26-4-1BBL, CT26-OX40L significantly inhibited the tumor growth compare with CT26-WT or CT26-β-gal cell line. These data showed the possibility the use of genetically modified tumor cells with costimulatory molecule as cancer immunotherapy agent.

• Genomics & Informatics
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• 제20권1호
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• pp.13.1-13.4
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• 2022

A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non-T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non-T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non-T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

• IMMUNE NETWORK
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• 제23권1호
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• pp.10.1-10.16
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• 2023

Memory T (Tm) cells protect against Ags that they have previously contacted with a fast and robust response. Therefore, developing long-lived Tm cells is a prime goal for many vaccines and therapies to treat human diseases. The remarkable characteristics of Tm cells have led scientists and clinicians to devise methods to make Tm cells more useful. Recently, Tm cells have been highlighted for their role in coronavirus disease 2019 vaccines during the ongoing global pandemic. The importance of Tm cells in cancer has been emerging. However, the precise characteristics and functions of Tm cells in these diseases are not completely understood. In this review, we summarize the known characteristics of Tm cells and their implications in the development of vaccines and immunotherapies for human diseases. In addition, we propose to exploit the beneficial characteristics of Tm cells to develop strategies for effective vaccines and overcome the obstacles of immunotherapy.

• 약학회지
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• 제48권6호
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• Molecules and Cells
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• 제20권2호
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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.