Association of cervical cancer with the presence of CD4+regulatory T cells specific for human papilomavirus antigens.journal article
Van der Burg SH, Piersma SJ, de Jong A, van der Hulst JM, Kwappenberg KM, van den Hende M, Welters MJ, Van Rood JJ, Fleuren GJ, Melief CJ, Kenter GG, Offringa R.
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12087-92.
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-gamma, 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.