Surgery followed by persistence of high-grade squamous intraepithelial lesions is associated with the induction of a dysfunctional HPV16-specific T-Cell response

Peggy J. De Vos Van Steenwijk, Sytse J. Piersma, Marij J.P. Welters, Jeanette M. Van Der Hulst, Gertjan Fleuren, Bart W.J. Hellebrekers, Gemma G. Kenter, Sjoerd H. Van Der Burg

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose: To characterize HPV16 E6- and E7-specific T-cell immunity in patients with high-grade squamous intraepithelial lesions (HSIL). Experimental Design: Peripheral blood mononuclear cells isolated from 38 patients with HPV16+ HSIL were used to determine the magnitude, breadth, and polarization of HPV16-specific T-cell responses by proliferation assays and cytokine assays. Furthermore, HSIL-infiltrating T cells isolated from 7 cases were analyzed for the presence of HPV16 E6- and/or E7-specific T cells, phenotyped, and tested for the specific production of IFN-γ and interleukin-10 as well as for their capacity to suppress immune responses. Results: HPV16-specific T-cell responses were absent in the circulation of the majority (f60%) of patients who visit the clinic for treatment of a HPV16+ HSIL lesion. Notably, HPV16-specific T-cell reactivity was predominantly detected in patients returning to the clinic for repetitive treatment of a persistent or recurrent HPV16+ HSIL lesion after initial destructive treatment. The majority (>70%) of these HPV16-specific T-cell responses did not secrete proinflammatory cytokines, indicating that most of the subjects, although in principle able to mount a HPV16-specific immune response, fail to develop protective cellular immunity. This notion is sustained by our observation that only three HSIL-infiltrating T-cell cultures contained HPV16-specific T cells, one of which clearly consisted of HPV16 E7-specific regulatory T cells. Conclusions: The presence of HPV16-specific T cells with a non-Th1/Th2 cytokine and even suppressive signature inpatients with HSIL may affect the outcome of vaccine approaches aiming at reinforcing human papillomavirus-specific immunity to attack human papillomavirus-induced lesions.

Original languageEnglish
Pages (from-to)7188-7195
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number22
DOIs
StatePublished - Nov 15 2008
Externally publishedYes

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