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Department of Medicine [E. M-l. E., S. M., L. K. B.], University of Wales College of Medicine, and Department of Obstetrics and Gynaecology [A. S. E.], University Hospital of Wales NHS Trust, Cardiff CF4 4XN, Wales, United Kingdom
CTLs specific for high-risk human papillomaviruses (HPVs) have recently been found in the peripheral blood of cervical cancer patients. Although cell-mediated immunity is thought to be important in the control of HPV infection, the functional relevance and site of activation of HPV-specific CTLs are unclear. We identified HLA-A*0201-restricted HPV-16 E7 peptide-specific CTLs in the peripheral blood (four of five patients), draining lymph nodes (three of four patients) and tumors (one of three patients) of cervical cancer patients. In four of four cancer patients, the frequency of CTLs specific for a recombinant vaccinia virus expressing HPV-16 and -18 E6/E7 gene products was found to be higher in tumors and lymph nodes compared with that of peripheral blood. HPV-specific CTLs were not identified in any of seven healthy controls, but primary responses could be generated by peptide-pulsed dendritic cells (four of four controls). In a non-HLA-A*0201 subject with invasive carcinoma, other HLA alleles also presented HPV antigens. This is the first demonstration that virus-specific CTLs infiltrate the virus-associated tumor, where they may play an important role in restricting disease progression.
1 Supported by the Medical Research Council, United Kingdom. E. M-l. E. is a Medical Research Council Clinical Training Fellow, and S. M. is a Royal Society University Research Fellow.
2 To whom requests for reprints should be addressed. Phone: 44-1222-745256; Fax: 44-1222-745003.
Received 1/17/97. Accepted 5/15/97.
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