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Article ; Online: Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells.

Lee, Young-Shin / Heo, Woong / Son, Cheol-Hun / Kang, Chi-Dug / Park, You-Soo / Bae, Jaeho

Molecular medicine reports

2019 Volume 20, Issue 4, Page(s) 3301–3307

Abstract: c‑Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c‑Myc proto‑oncogene is a common event in the development and growth of various human types of cancer, the present study ... ...

Abstract	c‑Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c‑Myc proto‑oncogene is a common event in the development and growth of various human types of cancer, the present study investigated whether oncogenic c‑Myc can alter natural killer (NK) cell‑mediated immunity through the expression of associated genes, using PCR, western blotting and flow cytometry assays. Furthermore, whether c‑Myc could influence the expression levels of natural killer group 2 member D (NKG2D) ligands, which are well known NK activation molecules, as well as NK cell‑mediated immunity, was investigated. c‑Myc was inhibited by 10058‑F4 treatment and small interfering RNA transfection. Upregulation of c‑Myc was achieved by transfection with a pCMV6‑myc vector. The inhibition of c‑Myc increased MHC class I polyeptide‑related sequence B and UL16 binding protein 1 expressions among NKG2D ligands, and the overexpression of c‑Myc suppressed the expression of all NKG2D ligands, except MHC class I polyeptide‑related sequence A. Furthermore, the alteration of c‑Myc activity altered the susceptibility of K562 cells to NK cells. These results suggested that the overexpression of c‑Myc may contribute to the immune escape of cancer cells and cell proliferation. Combined treatment with NK‑based cancer immunotherapy and inhibition of c‑Myc may achieve improved therapeutic results.
MeSH term(s)	Gene Expression Regulation, Leukemic/immunology ; Humans ; Immunity, Cellular ; K562 Cells ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; Proto-Oncogene Proteins c-myc/immunology ; Tumor Escape ; Up-Regulation/immunology
Chemical Substances	KLRK1 protein, human ; MYC protein, human ; NK Cell Lectin-Like Receptor Subfamily K ; Proto-Oncogene Proteins c-myc
Language	English
Publishing date	2019-08-09
Publishing country	Greece
Document type	Journal Article
ISSN	1791-3004
ISSN (online)	1791-3004
DOI	10.3892/mmr.2019.10583
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Enhancement of antitumor immunity by combination of anti-CTLA-4 antibody and radioimmunotherapy through the suppression of Tregs.

Son, Cheol-Hun / Bae, Jaeho / Lee, Hong-Rae / Yang, Kwangmo / Park, You-Soo

Oncology letters

2017 Volume 13, Issue 5, Page(s) 3781–3786

Abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in ... ...

Abstract	Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the
Language	English
Publishing date	2017-03-28
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2573196-8
ISSN	1792-1082 ; 1792-1074
ISSN (online)	1792-1082
ISSN	1792-1074
DOI	10.3892/ol.2017.5933
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Article ; Online: Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects.

Choi, Chul Won / Jeong, Min Ho / Park, You-Soo / Son, Cheol-Hun / Lee, Hong-Rae / Koh, Eun-Kyoung

Cancer research and treatment

2018 Volume 51, Issue 2, Page(s) 464–473

Abstract: Purpose: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with ... ...

Abstract	Purpose: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). Methods and materials: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system. Results: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group. Conclusion: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Combined Modality Therapy ; Cytokines/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Models, Animal ; Humans ; Immunotherapy ; Kaplan-Meier Estimate ; Mice ; Neoplasms/immunology ; Neoplasms/mortality ; Neoplasms/pathology ; Neoplasms/therapy ; Radiosurgery/methods ; Tumor Burden
Chemical Substances	Cancer Vaccines ; Cytokines
Language	English
Publishing date	2018-06-06
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2133613-1
ISSN	2005-9256 ; 1598-2998
ISSN (online)	2005-9256
ISSN	1598-2998
DOI	10.4143/crt.2018.186
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Article ; Online: Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Hong-Rae Lee / Cheol-Hun Son / Eun-Kyoung Koh / Jae-Ho Bae / Chi-Dug Kang / Kwangmo Yang / You-Soo Park

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 13

Abstract: Abstract Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells ... ...

Abstract	Abstract Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion. This method more potently expanded NK cells, and the final product was composed of highly purified NK cells with lesser T-cell contamination. The expanded NK cells showed greater upregulation of various activation receptors, CD107a, and secreted larger amounts of interferon gamma. IrAPs expressed NKG2D ligands and CD48, and coengagement of CD16 with NKG2D and 2B4 caused potent NK cell activation and proliferation. The expanded NK cells were cytotoxic toward various cancer cells in vitro and in vivo. Moreover, irradiation or a chemotherapeutic drug further enhanced this antitumor effect. Therefore, we developed an effective in vitro culture method for large-scale expansion of highly purified cytotoxic NK cells with potent antitumor activity using IrAPs instead of cancer cell-based feeder cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Functional Characterization of an

Son, Hyosuk / Jung, Young Jun / Park, Seong-Cheol / Kim, Il Ryong / Park, Joung Hun / Jang, Mi-Kyeong / Lee, Jung Ro

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 18

Abstract: Profilins (PFNs) are actin monomer-binding proteins that function as antimicrobial agents in plant phloem sap. Although the roles ... ...

Abstract	Profilins (PFNs) are actin monomer-binding proteins that function as antimicrobial agents in plant phloem sap. Although the roles of
MeSH term(s)	Actins/metabolism ; Antifungal Agents/metabolism ; Arabidopsis/metabolism ; Heat-Shock Response ; Microfilament Proteins/metabolism ; Molecular Chaperones/metabolism ; Plants/metabolism ; Profilins/genetics
Chemical Substances	Actins ; Antifungal Agents ; Microfilament Proteins ; Molecular Chaperones ; Profilins
Language	English
Publishing date	2022-09-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27185771
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Article ; Online: Amidoxime-Containing Zr and Hf Atomic Layer Deposition Precursors for Metal Oxide Thin Films.

Lee, Ga Yeon / Lee, Seung-Hun / Jo, In Ho / Cho, Chan-Mi / Shostak, Svetlana / Ryu, Ji Yeon / Park, Bo Keun / Son, Seung Uk / Choi, Cheol Ho / Eom, Taeyong / Kim, Jeong Hwan / Chung, Taek-Mo

Inorganic chemistry

2023 Volume 63, Issue 1, Page(s) 537–547

Abstract: In this article, we discuss the synthesis of eight novel zirconium and hafnium complexes containing amidoxime ligands as potential precursors for atomic layer deposition (ALD). Two amidoximes, ...

Abstract	In this article, we discuss the synthesis of eight novel zirconium and hafnium complexes containing amidoxime ligands as potential precursors for atomic layer deposition (ALD). Two amidoximes,
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1484438-2
ISSN	1520-510X ; 0020-1669
ISSN (online)	1520-510X
ISSN	0020-1669
DOI	10.1021/acs.inorgchem.3c03455
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Article ; Online: Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody.

Lee, Hong-Rae / Son, Cheol-Hun / Koh, Eun-Kyoung / Bae, Jae-Ho / Kang, Chi-Dug / Yang, Kwangmo / Park, You-Soo

Scientific reports

2017 Volume 7, Issue 1, Page(s) 11075

Abstract: Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most ... ...

Abstract	Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion. This method more potently expanded NK cells, and the final product was composed of highly purified NK cells with lesser T-cell contamination. The expanded NK cells showed greater upregulation of various activation receptors, CD107a, and secreted larger amounts of interferon gamma. IrAPs expressed NKG2D ligands and CD48, and coengagement of CD16 with NKG2D and 2B4 caused potent NK cell activation and proliferation. The expanded NK cells were cytotoxic toward various cancer cells in vitro and in vivo. Moreover, irradiation or a chemotherapeutic drug further enhanced this antitumor effect. Therefore, we developed an effective in vitro culture method for large-scale expansion of highly purified cytotoxic NK cells with potent antitumor activity using IrAPs instead of cancer cell-based feeder cells.
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Biomarkers ; CD48 Antigen/metabolism ; Cell Degranulation/drug effects ; Cell Degranulation/immunology ; Cell Degranulation/radiation effects ; Cell Line, Tumor ; Cytokines/biosynthesis ; Cytotoxicity, Immunologic ; Flow Cytometry ; Heterografts ; Humans ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/radiation effects ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Lymphocyte Activation/radiation effects ; Lysosomal-Associated Membrane Protein 1/metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Protein Binding ; Receptors, IgG/antagonists & inhibitors
Chemical Substances	Antibodies, Monoclonal ; Biomarkers ; CD48 Antigen ; Cytokines ; KLRK1 protein, human ; Lysosomal-Associated Membrane Protein 1 ; NK Cell Lectin-Like Receptor Subfamily K ; Receptors, IgG
Language	English
Publishing date	2017-09-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-09259-1
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Article ; Online: Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells.

Son, Cheol-Hun / Lee, Hong-Rae / Koh, Eun-Kyoung / Shin, Dong-Yeok / Bae, Jae-Ho / Yang, Kwangmo / Park, You-Soo

Scientific reports

2016 Volume 6, Page(s) 32470

Abstract: Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. ...

Abstract	Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- γ against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.
Language	English
Publishing date	2016-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep32470
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Article ; Online: Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines.

Lee, Banghyun / Chang, Suk-Joon / Kwon, Byung Su / Son, Joo-Hyuk / Lim, Myong Cheol / Kim, Yun Hwan / Lee, Shin-Wha / Choi, Chel Hun / Eoh, Kyung Jin / Lee, Jung-Yun / Suh, Dong Hoon / Kim, Yong Beom

Journal of gynecologic oncology

2023 Volume 35, Issue 1, Page(s) e43

Abstract: Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, ... ...

Abstract	Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.
MeSH term(s)	Female ; Humans ; Bevacizumab/adverse effects ; Carcinoma, Ovarian Epithelial/drug therapy ; Neoplasm Recurrence, Local/drug therapy ; Ovarian Neoplasms/drug therapy ; Republic of Korea
Chemical Substances	Bevacizumab (2S9ZZM9Q9V)
Language	English
Publishing date	2023-12-27
Publishing country	Korea (South)
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2024.35.e43
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Article ; Online: Combination effect of regulatory T-cell depletion and ionizing radiation in mouse models of lung and colon cancer.

Son, Cheol-Hun / Bae, Jae-Ho / Shin, Dong-Yeok / Lee, Hong-Rae / Jo, Wol-Soon / Yang, Kwangmo / Park, You-Soo

International journal of radiation oncology, biology, physics

2015 Volume 92, Issue 2, Page(s) 390–398

Abstract: Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy.: Methods and materials: We used LD-CTX and anti-CD25 monoclonal antibody ... ...

Abstract	Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.
MeSH term(s)	Animals ; Antineoplastic Agents, Alkylating/administration & dosage ; Colonic Neoplasms/immunology ; Colonic Neoplasms/mortality ; Colonic Neoplasms/radiotherapy ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Immunosuppressive Agents/administration & dosage ; Interleukin-2 Receptor alpha Subunit/antagonists & inhibitors ; Lung Neoplasms/immunology ; Lung Neoplasms/mortality ; Lung Neoplasms/radiotherapy ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/radiation effects
Chemical Substances	Antineoplastic Agents, Alkylating ; Immunosuppressive Agents ; Interleukin-2 Receptor alpha Subunit ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2015-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2015.01.011
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