Signaling defects and functional impairment in T-cells from cervical cancer patients

Cancer Biother Radiopharm. 2009 Dec;24(6):667-73. doi: 10.1089/cbr.2009.0660.

Abstract

The ability of T-lymphocytes to recognize antigens and transduce signals to the nucleus successfully is a key component in the initiation and maintenance of an immune response. The present study addressed the expression status of the signal-transducing proteins in relation to the immune impairment in cervical cancer patients. Immune response was measured by evaluating lymphocyte subpopulations CD3(+), CD4(+), and CD8(+), using flowcytometry, natural killer cell activity, using the single-cell cytotoxicity assay, lymphocyte function, using mitogenic response to PHA and T-cell activation following anti-CD3 stimulation, and production of IL-2. Expression of the T-cell signal transduction proteins, TCR-zeta, CD3-epsilon, zap-70, p(56)lck, PKC, NFkappabeta p50, Rel-A, Rel-B, and c-rel, was evaluated by using Western blot assay. A generalized depression of the immune response with respect to the different parameters evaluated was observed. Exogenous interleukin-2 (IL-2) could increase the response in all the controls and in 30% of the patients to different degrees varying from 10% to 90%. Low levels of the signaling molecules (TCR-zeta, CD3-epsilon, zap-70, p(56)lck, and PKC) and impairment in the transduction of NFkappabeta components (p50, Rel-A, Rel-B, and c-rel) to the nuclei were observed in these lymphocytes. Decreased CD4(+)/CD8(+) ratio with an increase in suppressor cells, reduced lymphocyte proliferation, and production of IL-2 suggest a defective immune regulation in cervical cancer. Impairment in the translocation of NFkappabeta p50, Rel-A, and Rel-B to the nucleus and the reduced levels of signal-transducing proteins might be responsible for the decreased production of IL-2 and immune impairment in cervical cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • CD3 Complex / immunology
  • Cell Division
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interleukin-2 / biosynthesis
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Lymphocytes / pathology
  • Middle Aged
  • Neoplasm Staging
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / physiopathology*

Substances

  • Antigens, CD
  • CD3 Complex
  • Interleukin-2