PMID- 16322265
OWN - NLM
STAT- MEDLINE
DCOM- 20060125
LR  - 20210103
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 23
DP  - 2005 Dec 1
TI  - Antitumor activity of human papillomavirus type 16 E7-specific T cells against 
      virally infected squamous cell carcinoma of the head and neck.
PG  - 11146-55
AB  - Human papillomavirus (HPV)-associated squamous cell carcinoma of the head and 
      neck (SCCHN) seems to be a suitable target for cancer vaccination. HPV-encoded 
      oncogenic proteins, such as E7, are promising tumor-specific antigens and are 
      obligatory for tumor growth. Because few immunologic studies have analyzed the 
      endogenous HPV-specific immune response in this subset of SCCHN patients, we 
      studied T-cell frequencies against HPV-16 E7(11-20) or E7(86-93) in 
      tumor-bearing, human leukocyte antigen (HLA)-A*0201+ SCCHN patients, whose tumors 
      were either HPV-16+ or HPV-16-. In HPV-16+ SCCHN patients, frequencies of T cells 
      against either peptide were significantly elevated (P < 0.005) compared with 
      HPV-16- patients or healthy volunteers. Tetramer+ T cells showed evidence of 
      terminally differentiated phenotype (CD45RA+CCR7-) and an elevated level of 
      CD107a staining for degranulation. Despite detectable expression of the 
      restricting HLA class I allele, HLA-A*0201-E7(11-20)- or 
      HLA-A*0201-E7(86-93)-specific CTL obtained by in vitro stimulation of healthy 
      donor peripheral blood mononuclear cells only recognize a naturally 
      HPV-16-transformed, HLA-A*0201+ SCCHN cell line after pretreatment with 
      IFN-gamma. This cell line had little or no expression of LMP2, TAP1, and tapasin, 
      critical components of the HLA class I antigen-processing machinery, which were 
      up-regulated by IFN-gamma treatment. Immunohistochemistry of HPV-16+ SCCHN tumors 
      showed that these antigen-processing machinery components are down-regulated in 
      tumors in vivo compared with adjacent normal squamous epithelium. Thus, immunity 
      to HPV-16 E7 is associated with the presence of HPV-16 infection and presentation 
      of E7-derived peptides on SCCHN cells, which show evidence of immune escape. 
      These findings support further development of E7-specific immunotherapy and 
      strategies for up-regulation of antigen-processing machinery components in 
      HPV-associated SCCHN.
FAU - Albers, Andreas
AU  - Albers A
AD  - Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, 
      Pennsylvania 15213, USA.
FAU - Abe, Koji
AU  - Abe K
FAU - Hunt, Jennifer
AU  - Hunt J
FAU - Wang, Jun
AU  - Wang J
FAU - Lopez-Albaitero, Andres
AU  - Lopez-Albaitero A
FAU - Schaefer, Carsten
AU  - Schaefer C
FAU - Gooding, William
AU  - Gooding W
FAU - Whiteside, Theresa L
AU  - Whiteside TL
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - DeLeo, Albert
AU  - DeLeo A
FAU - Ferris, Robert L
AU  - Ferris RL
LA  - eng
GR  - CA110249/CA/NCI NIH HHS/United States
GR  - CA67108/CA/NCI NIH HHS/United States
GR  - DE016406/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*immunology/therapy/*virology
MH  - Dendritic Cells/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HLA-A Antigens/immunology
MH  - HLA-A2 Antigen
MH  - Head and Neck Neoplasms/*immunology/therapy/*virology
MH  - Human papillomavirus 16/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/methods
MH  - Interferon-gamma/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Oncogene Proteins, Viral/*immunology
MH  - Papillomavirus E7 Proteins
MH  - Papillomavirus Infections/complications/immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2005/12/03 09:00
MHDA- 2006/01/26 09:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2006/01/26 09:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
AID - 65/23/11146 [pii]
AID - 10.1158/0008-5472.CAN-05-0772 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Dec 1;65(23):11146-55. doi: 10.1158/0008-5472.CAN-05-0772.