Association of cervical cancer with the presence of CD4⁺ regulatory T cells specific for human papillomavirus antigens
2007
van der Burg, Sjoerd H. | Piersma, Sytse J. | de Jong, Annemieke | van der Hulst, Jeanette M. | Kwappenberg, Kitty M.C. | van den Hende, Muriel | Welters, Marij J.P. | Rood, Jon J. van | Fleuren, Gert Jan | Melief, Cornelis J.M. | Kenter, Gemma G. | Offringa, Rienk
Because of their important role in the maintenance of self-tolerance, CD4⁺ regulatory T cells prevent autoimmune diseases but also curtail the efficacy of T cell immune responses against cancers. We now show that this suppressive action of CD4⁺ regulatory T cells is not limited to cancers displaying tumor-associated self antigens, such as melanomas, but also extends to human papillomavirus (HPV)-positive cervical cancers that express foreign tumor antigens. HPV-specific CD4⁺ T cells isolated from lymph node biopsies of cervical cancer patients were found to suppress proliferation and cytokine (IFN-γ, IL-2) production by responder T cells. The capacity of HPV-specific CD4⁺ T cells to exert this suppressive effect depended on their activation by cognate HPV antigen and on close-range interactions with responder T cells. HPV-specific CD4⁺ regulatory T cells were also retrieved from cervical cancer biopsies, suggesting that they interfere with the anti-tumor immune response at both the induction and effector levels. Our findings offer a plausible explanation for the observed failure of the tumor-specific immune response in patients with cervical carcinoma.
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