Association of cervical cancer with the presence of CD4 super(+) regulatory T cells specific for human papillomavirus antigens

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-07, Vol.104 (29), p.12087-12092
• Main Authors: van der Burg, Sjoerd H, Piersma, Sytse J, de Jong, Annemieke, van der Hulst, Jeanette M, Kwappenberg, Kitty MC, van den Hende, Muriel, Welters, Marij JP, Van Rood, Jon J, Fleuren, Gert Jan, Melief, Cornelis JM, Kenter, Gemma G, Offringa, Rienk
• Format: Article
• Language: English
• Subjects: Human papillomavirus
• ISSN: 0027-8424; 1091-6490

Because of their important role in the maintenance of self-tolerance, CD4 super(+) 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 super(+) 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 super(+) 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 super(+) 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 super(+) 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.