Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
August-2017 Volume 14 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2017 Volume 14 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression

  • Authors:
    • Rui Deng
    • Fang‑Yi Fan
    • Hai Yi
    • Li Fu
    • Yan Zeng
    • Yi Wang
    • Xiao‑Juan Miao
    • Yan‑Rong Shuai
    • Guang‑Cui He
    • Yi Su
  • View Affiliations / Copyright

    Affiliations: Department of Hematology and Hematopoietic Stem Cell Transplantation, Chengdu Military General Hospital of the People's Liberation Army, Chengdu, Sichuan 610083, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1081-1085
    |
    Published online on: June 16, 2017
       https://doi.org/10.3892/etm.2017.4620
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell‑specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte‑depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3+CD8+ CTLs through immune stimulation. These CD3+CD8+ CTLs could effectively recognize and induce the apoptosis of human Kasumi‑3 AML cells. In addition, cytarabine‑induced AML cell apoptosis was enhanced by CTL treatment. Western blotting revealed that Bcl‑2 expression was downregulated in AML cells following cytarabine and CTL treatment, indicating that the synergistic effect of this treatment on AML cell apoptosis is due to the downregulation of Bcl‑2. These results highlight the potential application of CTL immunotherapy for the treatment of AML. Further studies optimizing the specificity and potency of CTLs, and identifying favorable combinations with other chemotherapeutic drug are required.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, et al: Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: Results of the AML02 multicentre trial. Lancet Oncol. 11:543–552. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Niewerth D, Creutzig U, Bierings MB and Kaspers GJ: A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood. 116:2205–2214. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Couzin-Frankel J: Breakthrough of the year 2013. Cancer immunotherapy. Science. 342:1432–1433. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, Dohner K, Schlenk RF, Pollack JR, Dohner H and Bullinger L: Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches. Blood. 108:4109–4117. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Castella B, Vitale C, Coscia M and Massaia M: Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: From bench to bedside. Cell Mol Life Sci. 68:2419–2432. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Van Driessche A, Berneman ZN and Van Tendeloo VF: Active specific immunotherapy targeting the wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: Lessons from early clinical trials. Oncologist. 17:250–259. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Brossart P, Schneider A, Dill P, Schammann T, Grünebach F, Wirths S, Kanz L, Bühring HJ and Brugger W: The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res. 61:6846–6850. 2001.PubMed/NCBI

8 

Theobald M, Biggs J, Hernández J, Lustgarten J, Labadie C and Sherman LA: Tolerance to p53 by A2. 1-restricted cytotoxic T lymphocytes. J Exp Med. 185:833–841. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Burstein HJ and Schwartz RS: Molecular origins of cancer. N Engl J Med. 358:5272008. View Article : Google Scholar : PubMed/NCBI

10 

Berger C, Turtle CJ, Jensen MC and Riddell SR: Adoptive transfer of virus-specific and tumor-specific T cell immunity. Curr Opin Immunol. 21:224–232. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Brimnes MK, Gang AO, Donia M, Straten P Thor, Svane IM and Hadrup SR: Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and CD3/CD28 dynabead-induced T cell expansion. Cancer Immunol Immunother. 61:1221–1231. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Hirohashi Y, Torigoe T, Inoda S, Morita R, Kochin V and Sato N: Cytotoxic T lymphocytes: Sniping cancer stem cells. Oncoimmunology. 1:123–125. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Falkenburg JF, Wafelman AR, Joosten P, Smit WM, van Bergen CA, Bongaerts R, Lurvink E, van der Hoorn M, Kluck P, Landegent JE, et al: Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood. 94:1201–1208. 1999.PubMed/NCBI

14 

Yee C, Thompson J, Byrd D, Riddell SR, Roche P, Celis E and Greenberg PD: Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 99:pp. 16168–16173. 2002; View Article : Google Scholar : PubMed/NCBI

15 

Bracci L, Schiavoni G, Sistigu A and Belardelli F: Immune-based mechanisms of cytotoxic chemotherapy: Implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 21:15–25. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Ramakrishnan R, Huang C, Cho HI, Lloyd M, Johnson J, Ren X, Altiok S, Sullivan D, Weber J, Celis E and Gabrilovich DI: Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy. Cancer Res. 72:5483–5493. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Ramakrishnan R, Assudani D, Nagaraj S, Hunter T, Cho HI, Antonia S, Altiok S, Celis E and Gabrilovich DI: Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J Clin Invest. 120:1111–1124. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Shurin GV, Tourkova IL, Kaneno R and Shurin MR: Chemotherapeutic agents in noncytotoxic concentrations increase antigen presentation by dendritic cells via an IL-12-dependent mechanism. J Immunol. 183:137–144. 2009. View Article : Google Scholar : PubMed/NCBI

19 

English D and Andersen BR: Single-step separation of red blood cells. Granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll-Hypaque. J Immunol Methods. 5:249–252. 1974. View Article : Google Scholar : PubMed/NCBI

20 

Deng R, Wang SM, Yin T, Ye TH, Shen GB, Li L, Zhao JY, Sang YX, Duan XG and Wei YQ: Inhibition of tumor growth and alteration of associated macrophage cell type by an HO-1 inhibitor in breast carcinoma-bearing mice. Oncol Res. 20:473–482. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Kruger NJ: The Bradford Method for Protein Quantitation. Methods Mol Biol. 32:9–15. 1994.PubMed/NCBI

22 

Garnett CT, Schlom J and Hodge JW: Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: Effects of docetaxel on immune enhancement. Clin Cancer Res. 14:3536–3544. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Gelbard A, Garnett CT, Abrams SI, Patel V, Gutkind JS, Palena C, Tsang KY, Schlom J and Hodge JW: Combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augments CTL-mediated lysis. Clin Cancer Res. 12:1897–1905. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Gameiro SR, Caballero JA, Higgins JP, Apelian D and Hodge JW: Exploitation of differential homeostatic proliferation of T-cell subsets following chemotherapy to enhance the efficacy of vaccine-mediated antitumor responses. Cancer Immunol Immunother. 60:1227–1242. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Nowak AK, Robinson BW and Lake RA: Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res. 63:4490–4496. 2003.PubMed/NCBI

26 

Hill SC, Youde SJ, Man S, Teale GR, Baxendale AJ, Hislop A, Davies CC, Luesley DM, Blom AM, Rickinson AB, et al: Activation of CD40 in cervical carcinoma cells facilitates CTL responses and augments chemotherapy-induced apoptosis. J Immunol. 174:41–50. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Vanneman M and Dranoff G: Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 12:237–251. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Zhang T and Herlyn D: Combination of active specific immunotherapy or adoptive antibody or lymphocyte immunotherapy with chemotherapy in the treatment of cancer. Cancer Immunol Immunother. 58:475–492. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang WC, Bretzlaff W, et al: T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 122:3138–3148. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, Wang LL and Han WD: Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 23:184–191. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Deng R, Fan FY, Yi H, Fu L, Zeng Y, Wang Y, Miao XJ, Shuai YR, He GC, Su Y, Su Y, et al: Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression. Exp Ther Med 14: 1081-1085, 2017.
APA
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y. ... Su, Y. (2017). Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression. Experimental and Therapeutic Medicine, 14, 1081-1085. https://doi.org/10.3892/etm.2017.4620
MLA
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y., Miao, X., Shuai, Y., He, G., Su, Y."Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression". Experimental and Therapeutic Medicine 14.2 (2017): 1081-1085.
Chicago
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y., Miao, X., Shuai, Y., He, G., Su, Y."Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression". Experimental and Therapeutic Medicine 14, no. 2 (2017): 1081-1085. https://doi.org/10.3892/etm.2017.4620
Copy and paste a formatted citation
x
Spandidos Publications style
Deng R, Fan FY, Yi H, Fu L, Zeng Y, Wang Y, Miao XJ, Shuai YR, He GC, Su Y, Su Y, et al: Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression. Exp Ther Med 14: 1081-1085, 2017.
APA
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y. ... Su, Y. (2017). Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression. Experimental and Therapeutic Medicine, 14, 1081-1085. https://doi.org/10.3892/etm.2017.4620
MLA
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y., Miao, X., Shuai, Y., He, G., Su, Y."Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression". Experimental and Therapeutic Medicine 14.2 (2017): 1081-1085.
Chicago
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., Wang, Y., Miao, X., Shuai, Y., He, G., Su, Y."Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression". Experimental and Therapeutic Medicine 14, no. 2 (2017): 1081-1085. https://doi.org/10.3892/etm.2017.4620
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team