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Heusinkveld, M.; Welters, M.J.P.; Poelgeest, M.I.E. van; Hulst, J.M. van der; Melief, C.J.M.; Fleuren, G.J.J.; ... ; Burg, S.H. van der (2011)

The detection of circulating human papillomavirus-specific T cells is associated with improved survival of patients with deeply infiltrating tumors

Article / Letter to editor
A detailed analyses of HPV-specific immunity was performed in a large group of patients with HPV-induced cervical cancer (CxCa) in relation to HLA-types and prognostic factors. Patients were HLA-typed and HPV16/18-specific T-cell immunity was assessed by proliferation assay and cytometric bead array using freshly isolated PBMC and by phenotypic analysis of HPV-specific T cells. The results were analyzed in relation to known disease-related HLA-types (DR7, DR13, DR15/DQ06), invasion-depth and size of tumor, lymph node (LN) status and disease free survival. In total 119 HLA-typed patients with CxCa were analyzed. Patients expressing the HLA-DR13 haplotype were underrepresented as compared to the Dutch population (p = 0.014), whereas HLA-DR7 was overrepresented in patients with HPV16+ CxCa (p = 0.006). In 29 of 94 patients (31%) from whom blood could be tested, a proliferative response to HPV16/18 was detected, which was associated with increased numbers of HPV-specific CD4+CD25+ ...Show moreA detailed analyses of HPV-specific immunity was performed in a large group of patients with HPV-induced cervical cancer (CxCa) in relation to HLA-types and prognostic factors. Patients were HLA-typed and HPV16/18-specific T-cell immunity was assessed by proliferation assay and cytometric bead array using freshly isolated PBMC and by phenotypic analysis of HPV-specific T cells. The results were analyzed in relation to known disease-related HLA-types (DR7, DR13, DR15/DQ06), invasion-depth and size of tumor, lymph node (LN) status and disease free survival. In total 119 HLA-typed patients with CxCa were analyzed. Patients expressing the HLA-DR13 haplotype were underrepresented as compared to the Dutch population (p = 0.014), whereas HLA-DR7 was overrepresented in patients with HPV16+ CxCa (p = 0.006). In 29 of 94 patients (31%) from whom blood could be tested, a proliferative response to HPV16/18 was detected, which was associated with increased numbers of HPV-specific CD4+CD25+ (activated) T cells (p = 0.03) and HPV-specific CD4+CD25+FoxP3-positive T cells (p = 0.04). The presence of both FoxP3-positive and negative HPV-specific CD4+CD25+ T cells was significantly correlated (p = 0.01). Interestingly, the detection of HPV-specific proliferation was associated with invasion depth (p = 0.020) but not with HLA type, tumor size nor LN status. Moreover, the detection of HPV-specific immunity was associated with an improved disease free survival (p = 0.04) in patients with deeply infiltrating tumors. In conclusion, HPV-specific proliferative T-cell response, comprising higher percentages of HPV-specific CD25+ and CD25+FoxP3-positive CD4+T cells, are more frequently detected in patients with deep infiltrating CxCa tumors and associated with an improved survival.Show less
human papillomavirus immunity prognosis T cells cervical cancer cervical-cancer patients intraepithelial neoplasia healthy-subjects helper immunity hla type-16 progression antigens lesions women
All authors
Heusinkveld, M.; Welters, M.J.P.; Poelgeest, M.I.E. van; Hulst, J.M. van der; Melief, C.J.M.; Fleuren, G.J.J.; Kenter, G.G.; Burg, S.H. van der
Date
2011-01-15
Journal
International Journal of Cancer
Volume
128
Issue
2
Pages
379 - 389
DOI
doi:10.1002/ijc.25361