PMID- 17724722
OWN - NLM
STAT- MEDLINE
DCOM- 20071130
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 121
IP  - 12
DP  - 2007 Dec 15
TI  - 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.
PG  - 2711-5
AB  - 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.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - de Boer, Marjon A
AU  - de Boer MA
AD  - Department of Pathology, Leiden University Medical Center, Leiden, The 
      Netherlands. m.a.de_boer@lumc.nl
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
FAU - van Poelgeest, Mariette I E
AU  - van Poelgeest MI
FAU - van den Akker, Brendy E
AU  - van den Akker BE
FAU - van der Burg, Sjoerd H
AU  - van der Burg SH
FAU - Kenter, Gemma G
AU  - Kenter GG
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (DNA, Viral)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Antigen-Presenting Cells
MH  - CD8-Positive T-Lymphocytes/*immunology/*virology
MH  - Carcinoma/immunology/virology
MH  - DNA, Viral
MH  - Down-Regulation
MH  - Female
MH  - Histocompatibility Antigens Class I/*analysis
MH  - Histocompatibility Antigens Class II/analysis
MH  - Human papillomavirus 16/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Neoplasm Staging
MH  - Oncogene Proteins, Viral/analysis
MH  - Papillomavirus E7 Proteins
MH  - Papillomavirus Infections/complications/*immunology/virology
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Repressor Proteins/analysis
MH  - T-Lymphocytes, Cytotoxic/immunology/virology
MH  - *Transcription, Genetic
MH  - Tumor Virus Infections/complications/*immunology/virology
MH  - Up-Regulation
MH  - Uterine Cervical Neoplasms/*immunology/pathology/*virology
MH  - Viral Load
EDAT- 2007/08/29 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/08/29 09:00
PHST- 2007/08/29 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/08/29 09:00 [entrez]
AID - 10.1002/ijc.23035 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Dec 15;121(12):2711-5. doi: 10.1002/ijc.23035.