Home LiteratureArticle Details
PMID: 21614153 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Immunophenotyping at the time of diagnosis distinguishes two groups of nasopharyngeal carcinoma patients: implications for adoptive immunotherapy.

International journal of biological sciences ·Vol. 7 ·No. 5 ·2011-00-00 ·Pages 607-17

Li J, Chen QY, Mo H, Zhang YL, Huang ZF, Zeng YX

Abstract

Adoptive immunotherapy with EBV-specific CTLs (EBV-CTL) has been used to treat EBV-associated nasopharyngeal carcinoma (NPC) but only a fraction of the patients shows noticeable clinical response. Sixty-seven newly diagnosed NPC patients from 2005 to 2007 and 21 healthy donors were collected. Immunological parameters and immune function of PBMCs and EBV-CTL were analyzed by flow cytometer analysis (FACS) and ⁵¹Cr releasing experiment; Molecular characteristics on NPC tumor cells were investigated by immunochemical staining and statistic analysis. NPC patients can be classified into two groups based on the percentage of CD3+ T cells in peripheral blood before accepted any treatment, (>52.6%, mean-2SE from healthy controls, NPC Group 1; <52.6%, NPC Group 2). The patients in Group 2 showed a significant decrease of CD3+CD8+ T-cells, CD3+CD4+ T-cells and CD3+CD45RO+ memory T cells, and increase of CD3⁻CD16+ NK cells compared to Group 1 patients and healthy controls (P<0.001). EBV-specific T cell responses, were weaker in this group of patients and their tumor cells expressed lower levels of the EBV encoded latent membrane protein (LMP)-1 and HLA class II protein compared with the patients of NPC Group 1 (P<0.05). These findings demonstrate that NPC patients could be distinguished on the basis of their immune status which will affect the efficacy of EBV-CTL immunotherapy.

Keywords
EBV-specific CTL LMP1 NPC immunophenotype immunotherapy
MeSH Terms
Carcinoma/classification,immunology,therapy Cells, Cultured Cytokines/genetics,metabolism Female Herpesvirus 4, Human/immunology Humans Immunophenotyping Immunotherapy, Adoptive/methods,standards Leukocytes, Mononuclear/metabolism Lymphocyte Activation Male Middle Aged Nasopharyngeal Neoplasms/classification,immunology,therapy T-Lymphocytes, Cytotoxic/immunology Viral Matrix Proteins/metabolism
Chemicals
Cytokines EBV-associated membrane antigen, Epstein-Barr virus Viral Matrix Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li Jiang
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Chen Qiu-yan
Mo Haoyuan
Zhang Yi-lan
Huang Zhou-feng
Zeng Yi-xin
References (36)
36 references, click to expand
  1. Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases.
    Annu Rev Microbiol. 2000;54:19-48 PMID: 11018123
  2. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients.
    Blood. 2010 Feb 4;115(5):925-35 PMID: 19880495
  3. Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis of cytolytic effector cells.
    Arch Immunol Ther Exp (Warsz). 2006 Sep-Oct;54(5):323-33 PMID: 17031467
  4. Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression.
    J Immunother. 2004 May-Jun;27(3):184-90 PMID: 15076135
  5. EBV specific CTL: a model for immune therapy.
    Vox Sang. 1998;74 Suppl 2:497-8 PMID: 9704488
  6. Immunotherapy for Epstein-Barr virus-associated tumors.
    Leuk Lymphoma. 2004 Oct;45(10):1981-7 PMID: 15370241
  7. Impaired CTL recognition of cells latently infected with Kaposi's sarcoma-associated herpes virus.
    J Immunol. 2000 Aug 15;165(4):2077-83 PMID: 10925292
  8. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer.
    Blood. 2007 Oct 15;110(8):2838-45 PMID: 17609424
  9. Epstein-Barr virus in the pathogenesis of NPC.
    Semin Cancer Biol. 2002 Dec;12(6):431-41 PMID: 12450729
  10. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses.
    Blood. 2003 Sep 15;102(6):2292-9 PMID: 12763937
  11. The immune response to primary EBV infection: a role for natural killer cells.
    Br J Haematol. 2005 Apr;129(2):266-74 PMID: 15813855
  12. Cytometric bead array (CBA) for the measurement of cytokines in urine and plasma of patients undergoing renal rejection.
    Cytokine. 2005 Oct 7;32(1):45-50 PMID: 16153856
  13. Expression of immune-related molecules in primary EBV-positive Chinese nasopharyngeal carcinoma: associated with latent membrane protein 1 (LMP1) expression.
    Cancer Biol Ther. 2007 Dec;6(12):1997-2004 PMID: 18087217
  14. EBV infection of T cells: potential role in malignant transformation.
    Semin Cancer Biol. 1996 Aug;7(4):197-207 PMID: 8946604
  15. Epstein-Barr virus (EBV) and its associated human cancers--genetics, epigenetics, pathobiology and novel therapeutics.
    Front Biosci. 2006 Sep 01;11:2672-713 PMID: 16720343
  16. A simplified 51Cr-release assay for killer cells.
    J Immunol Methods. 1974 Mar;4(2):301-15 PMID: 4546189
  17. Epstein-Barr virus-specific cytotoxic T lymphocyte responses in the blood and tumor site of Hodgkin's disease patients: implications for a T-cell-based therapy.
    Cancer Res. 2001 Aug 15;61(16):6219-26 PMID: 11507075
  18. The role of Epstein-Barr virus in neoplastic transformation.
    Oncology. 2001;60(4):289-302 PMID: 11408795
  19. Analysis of tumor-host interactions by gene expression profiling of lung adenocarcinoma xenografts identifies genes involved in tumor formation.
    Mol Cancer Res. 2005 Mar;3(3):119-29 PMID: 15798092
  20. Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
    PLoS One. 2007 Nov 07;2(11):e1122 PMID: 17987110
  21. Immune responses against persistent viral infections: possible avenues for immunotherapeutic interventions.
    Crit Rev Immunol. 2008;28(2):159-83 PMID: 18540829
  22. Adoptive cell therapy against EBV-related malignancies: a survey of clinical results.
    Expert Opin Biol Ther. 2008 Sep;8(9):1265-94 PMID: 18694349
  23. Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways.
    Mol Cancer. 2010 Jan 10;9:4 PMID: 20064222
  24. Immunization with Epstein-Barr Virus (EBV) peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patients with EBV-positive nasopharyngeal carcinoma.
    Cancer Res. 2002 Dec 1;62(23):6952-8 PMID: 12460912
  25. Biological aspects of Epstein-Barr virus (EBV)-infected lymphocytes in chronic active EBV infection and associated malignancies.
    Crit Rev Oncol Hematol. 2002 Dec;44(3):239-49 PMID: 12467964
  26. Expression of tumor-associated Thomsen-Friedenreich antigen (T Ag) in Helicobacter pylori and modulation of T Ag specific immune response in infected individuals.
    Immunol Invest. 2002 Aug-Nov;31(3-4):191-204 PMID: 12472179
  27. Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma.
    Cancer. 2004 Mar 15;100(6):1162-70 PMID: 15022282
  28. The role of Epstein-Barr virus in cancer.
    Expert Opin Biol Ther. 2006 Nov;6(11):1193-205 PMID: 17049016
  29. Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas.
    Hematology Am Soc Hematol Educ Program. 2005;:260-6 PMID: 16304390
  30. Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients.
    Blood. 2009 Mar 12;113(11):2442-50 PMID: 18971421
  31. Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS).
    Pathol Res Pract. 1993 Sep;189(8):862-6 PMID: 8302707
  32. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes.
    J Clin Oncol. 2005 Dec 10;23(35):8942-9 PMID: 16204009
  33. Immune surveillance against Epstein-Barr virus.
    Semin Immunol. 1992 Apr;4(2):97-104 PMID: 1377517
  34. Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes.
    Blood. 2005 Mar 1;105(5):1898-904 PMID: 15542583
  35. Generation and maintenance of human memory cells during viral infection.
    Springer Semin Immunopathol. 2006 Nov;28(3):197-208 PMID: 16967292
  36. Lack of HLA class II antigen expression in microsatellite unstable colorectal carcinomas is caused by mutations in HLA class II regulatory genes.
    Int J Cancer. 2010 Aug 15;127(4):889-98 PMID: 20013806
Article Info
Journal
International journal of biological sciences
Abbr.
Int J Biol Sci
ISSN
1449-2288
Published
2011-00-00
Epub
2011-00-18
Pages
607-17
Language
English
Region
Australia
NLM ID
101235568
PMCID
PMC3101529
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com