Circulating human papillomavirus type 16 specific T-cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts.

Human papillomavirus (HPV) is a necessary factor in the pathogenesis of cervical cancer. Circulating HPV-specific T-cells responding to the E6 and E7 HPV proteins can be detected only in half of cervical cancer patients. Potential explanations for the absence of this response are lack of sufficient amounts of antigen to activate the immune response or local immune escape mechanisms. We studied the relationship between HPV 16 E6/E7 oncogene mRNA expression, human leukocyte antigen (HLA) expression on tumor cells and the presence of circulating E6- and E7-specific T-cell responses in cervical cancer patients. The amount of antigen was assessed by HPV E6/E7 mRNA expression levels measured by quantitative polymerase chain reaction. HLA Class I and Class II expression on tumor cells was analyzed by immunohistochemistry. A proliferative HPV-specific T-cell response was detected in 15/29 patients. The amount of HPV E6/E7 mRNA was not related to the presence of immune response. HLA Class I expression was downregulated in 19 patients and completely lost in 7 patients. HLA Class II expression was upregulated in 18 patients. HLA Class I expression on tumor cells showed a strong correlation with immunity (p = 0.001). Explicitly, all patients with complete HLA loss lacked HPV specific T-cell responses. The presence of circulating HPV-specific T-cells might reflect ongoing antitumor response that is sustained by CD8+ T-cells killing HLA Class I positive cancer cells. We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy.

de Boer MA ，Jordanova ES ，van Poelgeest MI ，van den Akker BE ，van der Burg SH ，Kenter GG ，Fleuren GJ ... -  《-》

Induction of human papillomavirus-specific CD4(+) and CD8(+) lymphocytes by E7-pulsed autologous dendritic cells in patients with human papillomavirus type 16- and 18-positive cervical cancer.

Santin AD ，Hermonat PL ，Ravaggi A ，Chiriva-Internati M ，Zhan D ，Pecorelli S ，Parham GP ，Cannon MJ ... -  《-》

Human papillomavirus type 16 (HPV-16) virus-like particle L1-specific CD8+ cytotoxic T lymphocytes (CTLs) are equally effective as E7-specific CD8+ CTLs in killing autologous HPV-16-positive tumor cells in cervical cancer patients: implications for L1 den

Bellone S ，El-Sahwi K ，Cocco E ，Casagrande F ，Cargnelutti M ，Palmieri M ，Bignotti E ，Romani C ，Silasi DA ，Azodi M ，Schwartz PE ，Rutherford TJ ，Pecorelli S ，Santin AD ... -  《-》

Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine.

Welters MJ ，Kenter GG ，Piersma SJ ，Vloon AP ，Löwik MJ ，Berends-van der Meer DM ，Drijfhout JW ，Valentijn AR ，Wafelman AR ，Oostendorp J ，Fleuren GJ ，Offringa R ，Melief CJ ，van der Burg SH ... -  《CLINICAL CANCER RESEARCH》

Optimal induction of HPV DNA vaccine-induced CD8+ T cell responses and therapeutic antitumor effect by antigen engineering and electroporation.

Seo SH ，Jin HT ，Park SH ，Youn JI ，Sung YC ... -  《-》