• Title, Summary, Keyword: tumor immunotherapy

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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.

Review of Tumor Dormancy Therapy Using Traditional Oriental Herbal Medicine

  • Lee, Jong-Ho;Koung, Fan-Pei;Cho, Chong-Kwan;Lee, Yeon-Weol;Yoo, Hwa-Seung
    • Journal of Pharmacopuncture
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    • v.16 no.1
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    • pp.12-20
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    • 2013
  • Objective: Standard cancer therapy prolongs survival, but can be detrimental to the quality of life, compromise the immune system, and leave residual disease that can cause recurrence years or decades in the future. Tumor dormancy therapy is a novel therapeutic approach that may improve these shortcomings, promote quality of life, and prolong survival. The aim of this study was to analyze studies on dormancy therapy, especially studies using traditional Oriental herbal medicine, so as to evaluate the efficacy of dormancy therapy with traditional oriental herbal medicine. Methods: We conducted a systematic literature review using Scientific and Technical Information Integration Services (NDSL), PubMed, and RISS. We searched for clinical reports, papers, and books related to tumor metastasis, recurrence, immunotherapy, tumor dormancy, and traditional oriental herbal medicine with anticancer effects. Seventy-nine (79) experimental and clinical articles in both Korean and English were reviewed. This study was conducted from March 1, 2012 to May 31, 2012. Results: This approach, Tumor dormancy therapy, rather than seeking to remove the tumor, includes combination of low-dose chemotherapy, immunotherapy, immunosurveillance, and other methods to stabilize tumor growth and to enhance the host is immunity against disseminated tumor cells and thus to manage cancer as a chronic disease while maintaining quality of life. In particular, integrative use of Oriental herbal medicine has been shown to induce or maintain tumor dormancy, increase the effectiveness of conventional chemotherapy, improve quality of life, and prolong survival. Conclusion: Tumor dormancy therapy is a promising novel therapeutic approach that may be especially effective with Oriental herbal medicine. Further research is needed to determine its potential mechanisms and therapeutic applications.

Single-Cell Sequencing in Cancer: Recent Applications to Immunogenomics and Multi-omics Tools

  • Sierant, Michael C.;Choi, Jungmin
    • Genomics & Informatics
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    • v.16 no.4
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    • pp.17.1-17.6
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    • 2018
  • Tumor heterogeneity, the cellular mosaic of multiple lineages arising from the process of clonal evolution, has continued to thwart multi-omics analyses using traditional bulk sequencing methods. The application of single-cell sequencing, in concert with existing genomics methods, has enabled high-resolution interrogation of the genome, transcriptome, epigenome, and proteome. Applied to cancers, these single-cell multi-omics methods bypass previous limitations on data resolution and have enabled a more nuanced understanding of the evolutionary dynamics of tumor progression, immune evasion, metastasis, and treatment resistance. This review details the growing number of novel single-cell multi-omics methods applied to tumors and further discusses recent discoveries emerging from these approaches, especially in regard to immunotherapy.

Identification of neoantigens derived from alternative splicing and RNA modification

  • Park, Jiyeon;Chung, Yeun-Jun
    • Genomics & Informatics
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    • v.17 no.3
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    • pp.23.1-23.6
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    • 2019
  • The acquisition of somatic mutations is the most common event in cancer. Neoantigens expressed from genes with mutations acquired during carcinogenesis can be tumor-specific. Since the immune system recognizes tumor-specific peptides, they are potential targets for personalized neoantigen-based immunotherapy. However, the discovery of druggable neoantigens remains challenging, suggesting that a deeper understanding of the mechanism of neoantigen generation and better strategies to identify them will be required to realize the promise of neoantigen-based immunotherapy. Alternative splicing and RNA editing events are emerging mechanisms leading to neoantigen production. In this review, we outline recent work involving the large-scale screening of neoantigens produced by alternative splicing and RNA editing. We also describe strategies to predict and validate neoantigens from RNA sequencing data.

Antitumor Responses of Adoptively-Transferred Tumor-Specific T-Cell Cultures in a Murine Lymphoma Model

  • Kim, Hee-Sue;Lee, Hee-Gu;Lim, Jong-Seok;Lee, Ki-Young;Kim, Jae-Wha;Chung, Kyeong-Soo;Choe, Yong-Kyung;Choe, In-Seong;Chung, Tai-Wha;Kim, Kil-Hyoun
    • BMB Reports
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    • v.28 no.6
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    • pp.556-561
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    • 1995
  • The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

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Dendritic Cell Based Cancer Immunotherapy: in vivo Study with Mouse Renal Cell Carcinoma Model (수지상세포를 이용한 항암 면역 치료: 생쥐 신장암 모델을 이용한 연구)

  • Lee, Hyunah;Choi, Kwang-Min;Baek, Soyoung;Lee, Hong-Ghi;Jung, Chul-Won
    • IMMUNE NETWORK
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    • v.4 no.1
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    • pp.44-52
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    • 2004
  • Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

The Analysis of Post Operative Treatment of Malignant Melanoma Using High Dose Interferon-${\alpha}2b$ Immunotherapy: Preliminary Report (악성흑색종 환자군에서 수술적 치료 후 시행한 고용량 인터페론-${\alpha}2b$ 면역요법에 의한 보조적 치료 결과 분석: 예비보고)

  • Chung, So Hak;Jo, Hyun Ik
    • The Journal of the Korean bone and joint tumor society
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    • v.18 no.2
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    • pp.78-82
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    • 2012
  • Purpose: Interferon-${\alpha}2b$ using immunotherapy of malignant melanoma is known to increase the microscopic enemies that remain after surgical resection of the tumor to prevent recurrence, disease-free survival and overall survival. Authors in patients with malignant melanoma after surgical resection and high-dose interferon-${\alpha}$ immunotherapy treated group of disease-free survival and overall survival compared with the results of the treatment of immune therapy to a preliminary report. Materials and Methods: From February 2010 to October 2012 at our institution between being diagnosed with malignant melanoma after surgical immunotherapy treated patients were analyzed. Patients was evaluated using the stage AJCC stage IIA 3 cases, IIB 1 cases, IV 1 were as follows. Follow-up period of at least 7 months, and a maximum of 32 months. As maintenance therapy after the first induction therapy group underwent immunotherapy interferon-${\alpha}$ of body-surface area per 200,000 IU five times in a week for 4 weeks sedentary and body surface area a total of 48 weeks per week to 100,000 IU three times subcutaneously. These patients for local recurrence and metastases, and distant metastasis were investigated disease-free survival was investigated. Results: Interferon-evaluation through follow-up chest computed tomography (CT) and positron emission computed tomography (PET CT) in patients who underwent the ${\alpha}$ immunotherapy results above both local recurrence and metastases without evidence of distant metastases. Conclusion: The high-dose ${\alpha}2b$ immunotherapy performed in patients to prevent the local recurrence of the tumor and metastasis to the current or future ultimate survival and disease-free survival improvement achieved is additional study and follow-up will be needed.

Anticancer Effect of Activated Natural Killer Cells on Human Non-small Cell Lung Cancer (비소세포성폐암에 대한 자연살해세포의 항암효능)

  • Park, Min-Gyeong;Sung, Hye-Ran;Park, Ji-Sung;Kim, Jee-Youn;Han, Sang-Bae;Lee, Chong-Kil;Yun, Byung-Kui;Song, Suk-Gil
    • YAKHAK HOEJI
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    • v.55 no.3
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    • pp.267-272
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    • 2011
  • Human NK cells, identified 30 years ago based on their ability to spontaneously kill tumor cells, constitute a subset of lymphocytes, which play an important role in the first line of immune defense and the effective function of these cells are enhanced by cytokines. Lung carcinoma has been one of the most commonly diagonosed cancer as well as the leading cause of cancer death in male. Here we provide the evidence that human natural killer cells has inhibitory effects on tumor growth of human lung cancer cell NCI-H460 (non-small cell lung cancer). Enriched NK cell population was obtained by 2 weeks cultivation in interleukin-2(IL-2)-containing medium. The resulting population comprised 26% CD3$^+$ cells, 9% CD3$^+$CD4$^+$ cells, 16% CD3$^+$CD8$^+$ cells, 76% CD56$^+$ cells, 6% CD3$^+$CD56$^+$ cells and 70% CD3$^-$CD56$^+$ cells. Activated NK cells at doese of 2.5, 5, and 10 million cells per mouse inhibited 2%, 12% and 45% of NCI-H460-induced tumor growth in nude mouse xenograft assays, repectively. This result suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for lung cancer patients.

Anticancer Effect of Activated Natural Killer Cells on Human Colorectal Tumor (결장암에 대한 활성 자연살해세포의 항암효능)

  • Sung, Hye-Ran;Kim, Jee-Youn;Park, Min-Gyeong;Kim, Il-Hoi;Lee, Dong-Wook;Han, Sang-Bae;Lee, Chong-Kil;Song, Suk-Gil
    • YAKHAK HOEJI
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    • v.54 no.3
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    • pp.192-199
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    • 2010
  • Colorectal cancer is one of the most common alimentary malignancies. In this study, the antitumor activity of activated human natural killer (NK) cells against human colorectal cancer was evaluated in vivo. Human NK cells are the key contributors of innate immune response and the effective functions of these cells are enhanced by cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured with interleukin-2 (IL-2)-containing medium for 14 days and resulted in enriched NK cell population. The resulting populations of the cells comprised 7% $CD3^+CD4^+$ cells, 25% $CD3^+CD8^+$ cells, 13% $CD3^-CD8^+$ cells, 4% $CD3^+$CD16/$CD56^+$ cells, 39% $CD3^+$CD16/$CD56^-$ cells, and 52% $CD3^-$CD16/$CD56^+$ cells. Tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), IL-2, IL-4, and IL-5 transcripts of the activated NK cells were confirmed by RT-PCR. In addition, activated NK cells at doses of 2.5, 5 and 10 million cells per mouse inhibited 10%, 34% and 47% of SW620-induced tumor growth in nude mouse xenograft assays, respectively. This study suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for colorectal cancer patients.

Potential Hypersensitivity of Recombinant Mouse IL-2 as a Immunotherapeutic Agent of Cancer in Tumor-bearing BALB/c Mice (항암 면역요법제 인터루킨-2의 면역과민반응 평가연구)

  • Cho, Young-Joo;Eom , Juno H.;Gil , Jung-Hyun;Park , Jae-Hyun;Lee , Jong-Kwon;Oh , Hye-Young;Park , Kui-Lea;Kim , Hyung-Soo
    • YAKHAK HOEJI
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    • v.48 no.6
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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.