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

Cheriyan, Vino T., Krishna, Smriti M., Kumar, Aswin, Jayaprakash, Puthuveetil Govindan, and Balaram, Prabha (2009) Signaling defects and functional impairment in T-cells from cervical cancer patients. Cancer Biotherapy and Radiopharmaceuticals, 24 (6). pp. 667-673.

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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-ζ, CD3-ɛ, zap-70, p56lck, PKC, NFκβ 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-ζ, CD3-ɛ, zap-70, p56lck, and PKC) and impairment in the transduction of NFκβ 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 NFκβ 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.

Item ID: 33994
Item Type: Article (Research - C1)
ISSN: 1557-8852
Funders: Kerala State Council for Science, Technology, and Environment , India, Tata Memorial Trust
Date Deposited: 23 Jul 2014 01:26
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 15%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060506 Virology @ 15%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 70%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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