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

Int J Biol Sci. 2011;7(5):607-17. doi: 10.7150/ijbs.7.607. Epub 2011 May 18.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / classification
  • Carcinoma / immunology*
  • Carcinoma / therapy
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunophenotyping*
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / standards
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / classification
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Matrix Proteins / metabolism

Substances

  • Cytokines
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Viral Matrix Proteins