Prostate specific antigen inhibits immune responses in vitro: a potential role in prostate cancer

AG Kennedy-Smith, JL McKenzie, MC Owen… - The Journal of …, 2002 - auajournals.org
AG Kennedy-Smith, JL McKenzie, MC Owen, PJT Davidson, S Vuckovic, DNJ Hart
The Journal of urology, 2002auajournals.org
Purpose: Prostate specific antigen (PSA) is found in high concentration in prostate tissue
and in semen, in which its physiological function appears to be liquefaction. In prostate
cancer the peripheral PSA concentration is elevated, which may be used as a disease
marker. Systemic and local immune defects have been demonstrated in prostate cancer and
we postulated a role for PSA in this immunosuppression. We explored the effects of PSA on
human T-lymphocyte proliferation in vitro. Materials and Methods: PSA was purified from …
Purpose
Prostate specific antigen (PSA) is found in high concentration in prostate tissue and in semen, in which its physiological function appears to be liquefaction. In prostate cancer the peripheral PSA concentration is elevated, which may be used as a disease marker. Systemic and local immune defects have been demonstrated in prostate cancer and we postulated a role for PSA in this immunosuppression. We explored the effects of PSA on human T-lymphocyte proliferation in vitro.
Materials and Methods
PSA was purified from normal seminal plasma using a modified chromatographic technique. The effect of PSA or control protein on lymphocyte responses to mitogens, tetanus toxoid and alloantigens was tested. The inhibitory effect observed was further explored by varying the time of PSA addition, denaturing PSA and including interleukin-2 and anti-PSA antibodies.
Results
PSA suppressed in vitro phytohemagglutinin and alloantigen stimulated lymphocyte proliferation in a dose dependent manner. This effect was reversed by adding anti-PSA antibodies but not by interleukin-2.
Conclusions
These in vitro PSA effects suggest another T-lymphocyte mediated immunosuppressive mechanism. In vivo high levels of PSA may compromise natural immune responses to cancer and current attempts at immunotherapy for prostate cancer.
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