| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Produced by Human Papilloma Virus-18 E6-Specific CD4+ T Cells Predicts the Clinical Outcome after Surgery in Patients with High-Grade Cervical Lesions1
* Tumor Immunology Unit,
Clinica Ostetrica e Ginecologica Università Vita-Salute San Raffaele,
Laboratory of Virology,
Unità Operativa Anatomia Patologica,
¶ Cancer Immunotherapy and Gene Therapy Program, and
|| Department of Oncology, Scientific Institute H. San Raffaele, Milan, Italy;
# MOX–Dipartimento di Matematica, Politecnico di Milano, Milan, Italy; and
** CNR-Istituto di Chimica del Riconoscimento Molecolare, Milan, Italy
Cervical neoplastic lesions are associated with infection by high-risk human papilloma viruses (HPVs). HPV-16 and HPV-18 are the most common genotypes. It has been proposed that development of HPV-16-positive cervical lesions is associated with impaired CD4+ T cell immunity against early Ags. The aim of the study was to evaluate whether this impairment also applies to HPV-18. We investigated the presence and the quality of anti-HPV-18 E6 CD4+ T cell responses in the blood of 37 consecutive patients with high-grade cervical lesions, 25 normal donors, and 20 cord bloods. The immune infiltrate in the cervical lesions was also evaluated. The characteristics of the responses were correlated to the clinical outcome. We found that one or more HPV-18 E6 peptides, containing naturally processed epitopes, were able to induce a response in 40–50% of the patients, depending on the effector function tested. Importantly, these percentages rose to 80–100% when HPV-18-positive patients were considered. HPV-18 E6-specific CD4+ T cells produced mixed Th1/Th2 responses and statistical analysis of the cytokines produced revealed that the amount of IFN-
released could predict infection persistence and/or disease relapse after surgery. Finally, we found that a higher number of infiltrating CD4+ and T-bet+ T cells in the lesions correlated with a favorable clinical outcome. Our results strongly suggest a relevant role for CD4+ T cells in the control of the HPV-18 compared with HPV-16 infections in patients with high-grade cervical lesions and identify an immunologic parameter potentially useful for patients’ stratification.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Cancer Research Institute (Clinical Investigation grant), the Italian Association for Cancer Research, the European Community (DC-THERA), the Compagnia di San Paolo, the Fondazione CARIPLO, and the Italian Ministry of Health.
2 M.O. and F.L. equally contributed to the work.
3 Current address: Fondazione Istituto San Raffaele G. Giglio di Cefalù, Palermo, Italy.
4 Address correspondence and reprint requests to Dr. Maria Pia Protti, Cancer Immunotherapy and Gene Therapy Program, DIBIT, Scientific Institute H. San Raffaele, Via Olgettina 58, 20132 Milan, Italy. E-mail address: m.protti{at}hsr.it
5 Abbreviations used in this paper: HPV, human papilloma virus; CIN, cervical intraepithelial neoplasia; HC2, hybrid capture 2; TCM, tissue-culture medium.
This article has been cited by other articles:
|
|
 |
|
  S. I. Collins, C. Constandinou-Williams, K. Wen, L. S. Young, S. Roberts, P. G. Murray, and C. B.J. Woodman Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study Cancer Res., May 1, 2009; 69(9): 3828 - 3832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tassi, F. Gavazzi, L. Albarello, V. Senyukov, R. Longhi, P. Dellabona, C. Doglioni, M. Braga, V. Di Carlo, and M. P. Protti Carcinoembryonic Antigen-Specific but Not Antiviral CD4+ T Cell Immunity Is Impaired in Pancreatic Carcinoma Patients J. Immunol., November 1, 2008; 181(9): 6595 - 6603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Guzman, A. Yambartsev, A. Goncalves-Primo, I. D.C.G. Silva, C. R.N. Carvalho, J. C.L. Ribalta, L. R. Goulart, N. Shulzhenko, M. Gerbase-DeLima, and A. Morgun New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer Hum. Mol. Genet., June 15, 2008; 17(12): 1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
