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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October 2012 Volume 4 Issue 4

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
October 2012 Volume 4 Issue 4

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

Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes

  • Authors:
    • Yoshiki Shigematsu
    • Takeshi Hanagiri
    • Hironobu Shiota
    • Koji Kuroda
    • Tetsuro Baba
    • Yoshinobu Ichiki
    • Manabu Yasuda
    • Hidetaka Uramoto
    • Mitsuhiro Takenoyama
    • Kosei Yasumoto
    • Fumihiro Tanaka
  • View Affiliations / Copyright

    Affiliations: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Yahatanishi 807‑8555, Japan
  • Pages: 625-630
    |
    Published online on: July 20, 2012
       https://doi.org/10.3892/ol.2012.815
  • 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

It is not easy to induce cytotoxic T lymphocytes (CTLs) against cancer in in vitro culture. Regulatory T cells (Tregs) are considered to play a pivotal role in tumor immune escape. In this study, we analyzed the distribution of Tregs among tumor‑infiltrating lymphocytes (TILs), regional lymph node lymphocytes (RLNLs) and peripheral blood lymphocytes (PBLs) in patients with lung cancer, and analyzed the effect of Tregs on the induction of CTLs in vitro. A total of 84 patients with non‑small cell lung cancer underwent surgery between January 2003 and December 2004. The TILs, RLNLs and PBLs from these patients were subjected to a comparison analysis. The proportion of CD4+CD25+Foxp3+ cells in these lymphocytes was determined by flow cytometry. The effects of Tregs on the induction of CTLs was analyzed by the depletion of Tregs in mixed lymphocyte‑tumor cell culture (MLTC). The average proportions of Tregs in the TILs, RLNLs and PBLs were 10.4±9.5, 4.4±2.4 and 2.8±2.1%, respectively. The proportion of Tregs in the RLNLs was significantly higher than that in the PBLs (P<0.001); furthermore, TILs contained a larger number of Tregs than RLNLs (P=0.034). These Tregs substantially suppressed the induction of CTLs against autologous tumor cells. The depletion of Tregs in the MLTC resulted in the successful induction of CTLs. Tregs were found at a higher frequency in the TILs and RLNLs than in the PBLs in lung cancer patients. Since Tregs inhibited the induction of CTLs, the depletion of Tregs may represent a new therapeutic strategy for lung cancer patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1. 

A JemalR SiegelE WardT MurrayJ XuMJ ThunCancer statistics, 2007CA Cancer J Clin574366200710.3322/canjclin.57.1.43

2. 

R SanghaC ButtsL-BLP25: a peptide vaccine strategy in non small cell lung cancerClin Cancer Res1346524654200710.1158/1078-0432.CCR-07-0213

3. 

J VansteenkisteM ZielinskiA LinderFinal results of a multi-center, double-blind, randomized, placebo-controlled Phase II study to assess the efficacy of MAGE-A3 immuno-therapeutic as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC)J Clin OncolSuppl 25398s2007

4. 

P van der BruggenC TraversariP ChomezA gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanomaScience254164316471991

5. 

Y IchikiM TakenoyamaM MizukamiSimultaneous cellular and humoral immune response against mutated p53 in a patient with lung cancerJ Immunol17248444850200410.4049/jimmunol.172.8.484415067062

6. 

M TakenoyamaJF BaurainM YasudaA point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytyic T lymphocytes on a human squamous cell lung carcinomaInt J Cancer11819921997200610.1002/ijc.2159416287085

7. 

F PagesA BergerM CamusEffector memory T cells, early metastasis, and survival in colorectal cancerN Engl J Med35326542666200510.1056/NEJMoa05142416371631

8. 

L ZhangJR Conejo-GarciaD KatsarosIntratumoral T cells, recurrence, and survival in epithelial ovarian cancerN Engl J Med348203213200310.1056/NEJMoa02017712529460

9. 

SA RosenbergJC YangNP RestifoCancer immunotherapy: moving beyond current vaccinesNat Med10909915200410.1038/nm110015340416

10. 

MK LevingsR SangregorioMG RoncaroloHuman cd25(+) cd4(+) t regulatory cells suppress naïve and memory T cell proliferation and can be expanded in vitro without loss of functionJ Exp Med193129513022001

11. 

EM ShevachCertified professionals: CD4(+)CD25(+) suppressor T cellsJ Exp Med1934146200111390442

12. 

H JonuleitE SchmittG SchulerJ KnopAH EnkInduction of interleukin 10-producing, non proliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cellsJ Exp Med192121312222000

13. 

S ReadF PowrieCD4(+) regulatory T cellsCurr Opin Immunol136446492001

14. 

AR GibbsFB ThunnissenHistological typing of lung and pleural tumours: third editionJ Clin Pathol54498499200110.1136/jcp.54.7.49811429418

15. 

CF MountainRevisions in the international system for staging lung cancerChest11117101717199710.1378/chest.111.6.17109187198

16. 

M SugayaM TakenoyamaT OsakiEstablishment of 15 cancer cell lines from patients with lung cancer and the potential tools for immunotherapyChest122282288200210.1378/chest.122.1.28212114371

17. 

M TakenoyamaI YoshinoR EifukuSuccessful induction of tumor-specific cytotoxic T lymphocytes from patients with non-small cell lung cancer using CD80-transfected autologous tumor cellsJpn J Cancer Res92309315200110.1111/j.1349-7006.2001.tb01096.x11267941

18. 

T FukuyamaY IchikiS YamadaCytokine production of lung cancer cell lines: correlation between their production and the inflammatory/immunological responses both in vivo and in vitroCancer Sci9810481054200710.1111/j.1349-7006.2007.00507.x

19. 

S SakaguchiM OnoR SetoguchiFoxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and auto-immune diseaseImmunol Rev2128272006

20. 

JD FontenotMA GavinAY RudenskyFoxp3 programs the development and function of CD4+CD25+ regulatory T cellsNat Immunol4330336200310.1038/ni90412612578

21. 

AM WolfD WolfM SteurerG GastlE GunsiliusB Grubeck-LoebensteinIncrease of regulatory T cells in the peripheral blood of cancer patientsClin Cancer Res9606612200312576425

22. 

LA OrmandyT HillemannH WedemeyerMP MannsTF GretenF KorangyIncreased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinomaCancer Res6524572464200510.1158/0008-5472.CAN-04-323215781662

23. 

EY WooCS ChuTJ GoletzRegulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancerCancer Res61476647722001

24. 

TJ CurielG CoukosL ZouSpecific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survivalNat Med10942949200410.1038/nm109315322536

25. 

GJ BatesSB FoxC HanQuantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapseJ Clin Oncol2453735380200610.1200/JCO.2006.05.958417135638

26. 

F GhiringhelliC MenardM TermeCD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-h-dependent mannerJ Exp Med20210751085200516230475

27. 

RP PetersenMJ CampaJ SperlazzaTumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patientsCancer10728662872200617099880

28. 

JC MarieJJ LetterioM GavinAY RudenskyTGF-beta 1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cellsJ Exp Med20110611067200510.1084/jem.2004227615809351

29. 

G WieczorekA AsemissenF ModelQuantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissueCancer Res69599608200910.1158/0008-5472.CAN-08-236119147574

30. 

TL WalunasCY BakkerJA BluestoneCTLA-4 ligation blocks CD28-dependent T cell activationJ Exp Med1832541255019968676075

31. 

MF KrummelJP AllisonCD28 and CTLA-4 have opposing effects on the response of T cells to stimulationJ Exp Med182459465199510.1084/jem.182.2.459

32. 

S ReadV MalmstromF PowrieCytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammationJ Exp Med1922953022000

33. 

B SalomonDJ LenschowL RheeB7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetesImmunity12431440200010.1016/S1074-7613(00)80195-810795741

34. 

NJ KarandikarCL VanderlugtTL WalunasSD MillerJA BluestoneCTLA-4: A negative regulator of autoimmune diseaseJ Exp Med184783788199610.1084/jem.184.2.7838760834

35. 

MC BrunnerCA ChambersFK ChanJ HankeA WinotoJP AllisonCTLA-4-Mediated inhibition of early events of T cell proliferationJ Immunol16258135820199910229815

36. 

DR LeachMF KrummelJP AllisonEnhancement of antitumor immunity by CTLA-4 blockadeScience27117341736199610.1126/science.271.5256.17348596936

37. 

A van ElsasAA HurwitzJP AllisonCombination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentationJ Exp Med1903553661999

38. 

A van ElsasRP SutmullerAA HurwitzElucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapyJ Exp Med1944814892001

39. 

FS HodiMC MihmRJ SoifferBiologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patientsProc Natl Acad Sci USA10047124717200310.1073/pnas.0830997100

40. 

GQ PhanJC YangRM SherryCancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanomaProc Natl Acad Sci USA10083728377200310.1073/pnas.153320910012826605

41. 

FS HodiM ButlerDA ObleImmunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patientsProc Natl Acad Sci USA10530053010200810.1073/pnas.071223710518287062

42. 

AJ KormanKS PeggsJP AllisonCheckpoint blockade in cancer immunotherapyAdv Immunol90297339200610.1016/S0065-2776(06)90008-X16730267

43. 

A RibasDC HansonDA NoeTremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancerOncologist12873883200710.1634/theoncologist.12-7-87317673618

44. 

T YamaguchiK HirotaK NagahamaControl of immune responses by antigen-specific regulatory T cells expressing the folate receptorImmunity27145159200710.1016/j.immuni.2007.04.01717613255

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Ichiki Y, Yasuda M, Uramoto H, Takenoyama M, Yasumoto K, Yasumoto K, et al: Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes. Oncol Lett 4: 625-630, 2012.
APA
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y. ... Tanaka, F. (2012). Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes. Oncology Letters, 4, 625-630. https://doi.org/10.3892/ol.2012.815
MLA
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y., Yasuda, M., Uramoto, H., Takenoyama, M., Yasumoto, K., Tanaka, F."Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes". Oncology Letters 4.4 (2012): 625-630.
Chicago
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y., Yasuda, M., Uramoto, H., Takenoyama, M., Yasumoto, K., Tanaka, F."Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes". Oncology Letters 4, no. 4 (2012): 625-630. https://doi.org/10.3892/ol.2012.815
Copy and paste a formatted citation
x
Spandidos Publications style
Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Ichiki Y, Yasuda M, Uramoto H, Takenoyama M, Yasumoto K, Yasumoto K, et al: Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes. Oncol Lett 4: 625-630, 2012.
APA
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y. ... Tanaka, F. (2012). Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes. Oncology Letters, 4, 625-630. https://doi.org/10.3892/ol.2012.815
MLA
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y., Yasuda, M., Uramoto, H., Takenoyama, M., Yasumoto, K., Tanaka, F."Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes". Oncology Letters 4.4 (2012): 625-630.
Chicago
Shigematsu, Y., Hanagiri, T., Shiota, H., Kuroda, K., Baba, T., Ichiki, Y., Yasuda, M., Uramoto, H., Takenoyama, M., Yasumoto, K., Tanaka, F."Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor‑specific cytotoxic T lymphocytes". Oncology Letters 4, no. 4 (2012): 625-630. https://doi.org/10.3892/ol.2012.815
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