Signaling defects and functional impairment in T-cells from cervical cancer patients.
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.
Cheriyan
Vino T
VT
Division of Cancer Research, Regional Cancer Center, Trivandrum, Kerala, India.
Krishna
Smriti M
SM
Kumar
Aswin
A
Jayaprakash
Puthuveetil Govindan
PG
Balaram
Prabha
P
D015703:Antigens, CD / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*
D015703:Antigens, CD; D017252:CD3 Complex; D007376:Interleukin-2