• Title/Summary/Keyword: Tumor immunity

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Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model: Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC

  • Baek, Soyoung;Lee, Seog Jae;Kim, Myoung Joo;Lee, Hyunah
    • IMMUNE NETWORK
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    • v.12 no.6
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    • pp.269-276
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    • 2012
  • The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

Evaluation of Anti-tumor Immunity in Cancer Patients through Peripheral Blood Natural Killer Cell Measurements: A Review (말초혈액 내 NK cell 측정을 통한 암환자의 종양 면역 기능 평가 가능성 고찰)

  • Jang, Sung-Il;Choi, Jung-Eun;Lee, Yeon-Weol;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • Journal of Haehwa Medicine
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    • v.21 no.1
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    • pp.87-96
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    • 2012
  • Aim : Natural killer (NK) cells are cytotoxic lymphocytes that lyse certain tumor- and virus-infected cells without any prior stimulation or immunization. This article aims to review the significance of evaluating peripheral blood NK cells to predict anti-tumor immune function and prognosis in cancer patients. Methods : PubMed was used to create a database for this review. Search words of cancer, natural killer cell, prognosis were used to retrieve related articles. References of the collected articles were also reviewed. Results : Current evidence indicates that decreased or absent NK cell count or activity is mostly associated with the development or progression of cancer. In patients with various types of cancer, NK cell activity was mostly associated with the cancer prognosis and survival despite some conflicting results. Conclusion : The data shows the evaluation of anti-tumor immunity in cancer patients through natural killer cell measurement still remains a controversial matter. However, it is clear that the NK cell activity plays an important role in cancer and is associated with prevention of both early stage and metastatic cancer.

IL-17-Producing Cells in Tumor Immunity: Friends or Foes?

  • Da-Sol Kuen;Byung-Seok Kim;Yeonseok Chung
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.6.1-6.20
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    • 2020
  • IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8+ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity

  • Guo, Jian;Qu, Huiheng;Shan, Ting;Chen, Yigang;Chen, Ye;Xia, Jiazeng
    • Molecules and Cells
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    • v.41 no.7
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    • pp.653-664
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    • 2018
  • The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

A literature study on oncological Immune therapy (암(癌)의 면역치료(免疫治療)에 대(對)한 고찰(考察))

  • Park, Jong-Hak;Son, Chang-Gyu;Cho, Chong-kwan
    • Journal of Haehwa Medicine
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    • v.9 no.2
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    • pp.211-221
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    • 2001
  • A literature study on oncological immune therapy was done, and the results were as follows. 1. Oncological immune therapy is classified as specific non specific therapy or active inactive therapy, and in tumor immune response, cellular immunity operates mainly, so activity of T lymphocytes and macrophages are closely related with growth, progress, metastasis and prospect of tumor. Recently, Immune therapies of gene which use cytokines and HLA-B7 are carrying out. 2. In oriental medicine, development of disease is closely related to up and down of healthy qi, so healthy qi operates as a immune factor and resistance factor. 3. On the base of theory "Increasing healthy qi reduces mass(養正則積自除)", strengthening body resistance is emphasized in cancer therapy. Also strengthening body resistance activates cellular immune response and promote killing tumor facility of T-cell. 4. In clinical view, using immune therapy after operation, radiation, and chemotheraphy is more effective than immune therapy itself, so it is expected that east-west cooperation will be effective in cancer therapy. 5. The study of oncological immunity is progressed on emphasizing T-cell and it is related to oriental medical theory "strengthening healthy qi to eliminate pathogen(扶定祛邪)" and advanced study is expected in future.

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Characterization of the CD11c Promoter Which Is Expressed in the Mouse Dendritic Cells (생쥐 수지상세포에서 발현하는 CD11c 프로모터의 규명)

  • Kim, Bon-Gi;Kim, Jung-Sik;Park, Chung-Gyu
    • IMMUNE NETWORK
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    • v.8 no.4
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    • pp.137-142
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    • 2008
  • Background: CD11c, also known as integrin alpha x, is one of the optimum markers of dendritic cells. However, the regulation of the CD11c expression in mouse has not been identified yet. In this study, in order to analyze the regulation of CD11c expression, the promoter of CD11c was cloned and characterized. Methods: To identify the promoter portion, various sizes of what are considered to be CD11c promoter fragments was amplified by polymerase chain reaction (PCR), using mouse genomic DNA as a template. After sequence was obtained, these fragments were transfected into various cell lines including mouse dendritic cell lines such as JAWSII and DC2.4 and L929 as control cell line.. The promoter activity of three promoter fragments was measured and compared by luciferase activity in the transfected cells. Results: Three clones with size of 1kb, 3kb and 6kb were obtained from mouse genomic DNA. Flow cytometry analysis of JAWSII cells revealed that 52% of the cells expressed CD11c, which was confirmed by RT-PCR analysis. On the contrary, L929 and DC 2.4 cells did not express CD11c. The CD11c+ JAWSII cells were enriched from 52% to 90% with cell sorter. The comparative luciferase activity analyisis demonstrated that the region responsible for tissue specific expression was contained within -3 kb and the clone with size of 3 kb particularly showed higher luciferase activity than 6 kb and 1 kb clones. Conclusion: The CD11c promoter region containing the region responsible for tissue specificity was successfully cloned and -3 kb region showed the highest activity.

The Production IL-21 and VEGF in UVB-irradiated Human Keratinocyte Cell Line, HaCaT

  • Kim, Hye-Min;Kang, Jae-Seung;Lee, Wang-Jae
    • IMMUNE NETWORK
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    • v.10 no.2
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    • pp.76-81
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    • 2010
  • Ultraviolet B (UVB) induces multiple inflammatory and carcinogenic reactions. In skin, UVB induces to secrete several kinds of inflammatory cytokines from keratinocytes and also increases angiogenic process via the modulation of vascular endothelial growth factor (VEGF) production. Interleukin-21 (IL-21) is an inflammatory cytokine and produced by activated T cells. The biologic functions of IL-21 have not yet extensively studied. In the present study, we investigate the production of IL-21 from human keratinocyte cell line, HaCaT and its biological effect after exposure to UVB. First, we confirmed the IL-21 production and its receptor expression in HaCaT. And then, the change of IL-21 and VEGF production in HaCaT by UVB irradiation was examined. Not only IL-21 but also VEGF production was enhanced by UVB irradiation. Next, to determine relationship of enhanced production of IL-21 and VEGF, we detected VEGF production after neutralization of IL-21. VEGF production was reduced by IL-21 neutralization, which indicates that the IL-21 is involved in the VEGF production. Taken together, our results suggest that IL-21 and VEGF production is enhanced by UVB irradiation in HaCaT. In addition, it seems that IL-21 plays a role in the angiogenic process in skin via the modulation of VEGF production.

Regulatory T Cells in Tumor Microenvironment and Approach for Anticancer Immunotherapy

  • Jung-Ho Kim;Beom Seok Kim;Sang-Kyou Lee
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.4.1-4.17
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    • 2020
  • Tregs have a role in immunological tolerance and immune homeostasis by suppressing immune reactions, and its therapeutic potential is critical in autoimmune diseases and cancers. There have been multiple studies conducted on Tregs because of their roles in immune suppression and therapeutic potential. In tumor immunity, Tregs can promote the development and progression of tumors by preventing effective anti-tumor immune responses in tumor-bearing hosts. High infiltration of Tregs into tumor tissue results in poor survival in various types of cancer patients. Identifying factors specifically expressed in Tregs that affect the maintenance of stability and function of Tregs is important for understanding cancer pathogenesis and identifying therapeutic targets. Thus, manipulation of Tregs is a promising anticancer strategy, but finding markers for Treg-specific depletion and controlling these cells require fine-tuning and further research. Here, we discuss the role of Tregs in cancer and the development of Treg-targeted therapies to promote cancer immunotherapy.