Augmentation of T-cell immune responses and signal transduction proteins in oral cancer patients: potential for IL-2-mediated immunotherapy.

Abstract

PURPOSE:

Immune impairment is hypothesized to be one of the reasons for the dismal treatment response in oral cancers. This study evaluates the immune impairment in patients with primary squamous cell carcinoma of the oral cavity and the effect of IL-2 administration on restoration of the immune responses.

METHODS:

T-cell populations were enumerated by flow cytometry; T-cell function by MTS proliferation assay to PHA and anti-CD3, expression of T-cell signaling proteins ZAP-70, TCRζ, p(56)lck, PKC and CD-ε in T cells with and without activation by IL-2 using Western blot and statistical analysis using X (2) test and bivariate correlation analysis in 112 patients.

RESULTS:

Reduction in proportion of CD3(+) and CD4(+) T lymphocytes, decrease in the CD4(+)/CD8(+) T-cell ratios, reduced lymphocyte transformation to PHA and anti-CD3 and reduced production of interleukin-2(IL-2) were observed in the patient group. Lymphocyte proliferation to anti-CD3 could be augmented in 59.5% of non-responders by IL-2 (range 10-90%) along with significant increase in the expression of TCR-ζ and ZAP-70, CD3ε, p(56) LCK and PKC to varying degrees. The expression of ZAP-70 and TCR-ζ was found to be closely related to treatment response and could be augmented by IL-2 in terms of proliferation and IL-2 production.

CONCLUSIONS:

The results suggest IL-2 to augment T-cell responses in a proportion of oral cancer patients with poor response to conventional therapy. IL-2 immunotherapy can be thought of as a personalized adjuvant therapy for oral cancer following the in vitro identification of IL-2 responders using the expression of TCRζ and ZAP-70 as biomarkers.

• Authors: Vino T Cheriyan, Cessal Thomas, Prabha Balaram
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 137 Issue 10 Pg. 1435-44 (Oct 2011) ISSN: 1432-1335 [Electronic] Germany
• PMID: 21809032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD3 Complex
• Interleukin-2
• Receptors, Antigen, T-Cell
• antigen T cell receptor, zeta chain
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
• ZAP-70 Protein-Tyrosine Kinase

Topics

• CD3 Complex (immunology)
• Humans
• Immunotherapy
• Interleukin-2 (metabolism, therapeutic use)
• Lymphocyte Activation
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (analysis)
• Mouth Neoplasms (immunology, therapy)
• Receptors, Antigen, T-Cell (analysis)
• Signal Transduction
• T-Lymphocytes (immunology)
• ZAP-70 Protein-Tyrosine Kinase (analysis)