Immunological Role of Dendritic Cells in Cervical Cancer
Cervical cancer is the second most frequent gynecological malignancy in the world. Human papillomavirus (HPV) infection is the primary etiologic agent of cervical cancer. However, HPV alone is not sufficient for tumor progression. The clinical manifestation of HPV infection depends also on the host’s immune status. Both innate and adaptive immunity play a role in controlling HPV infection. In untransformed HPV-infected keratinocytes, the innate immunity is induced to eliminate the invading HPV pathogen through sensitization to HPV-related proteins by epithelial-residing Langerhans cells (LCs), macrophages, and other immune cells. Once the HPV infection escapes from initial patrolling by innate immunity, cellular immunity becomes in charge of killing the HPV-infected keratinocytes of the uterine cervix through systemic immune response developing by dendritic cells (DCs) in the regional lymphoid organs or through local immune response developing by LCs in the cervix. Thereby, DC/LC plays a critical role in eliciting innate and adaptive cellular immune responses against HPV infection. HPV-associated cervical malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic vaccine clinical trials.
KeywordsCervical Cancer Cervical Intraepithelial Neoplasia Uterine Cervix Cervical Cancer Patient Systemic Immune Response
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- Adams, M., Navabi, H., Jasani, B., Man, S., Fiander, A., Evans, A. S., Donninger, C. and Mason, M. (2003) Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21, 787–790.CrossRefPubMedGoogle Scholar
- Borkowski, T. A., Van Dyke, B. J., Schwarzenberger, K., McFarland, V. W., Farr, A. G. and Udey, M. C. (1994) Expression of E-cadherin by murine dendritic cells: E-cadherin as a dendritic cell differentiation antigen characteristic of epidermal Langerhans cells and related cells. Eur. J. Immunol. 24, 2767–2774.CrossRefPubMedGoogle Scholar
- Del Mistro, A., Insacco, E., Cinel, A., Bonaldi, L., Minucci, D. and Chieco-Bianchi, L. (1994) Human papillomavirus infections of the genital region in human immunodeficiency virus seropositive women: integration of type 16 correlates with rapid progression. Eur. J. Gynaecol. Oncol. 15, 50–58.PubMedGoogle Scholar
- Eckert, L. O., Watts, D. H., Koutsky, L. A., Hawes, S. E., Stevens, C. E., Kuypers, J. and Kiviat, N. B. (1999) A matched prospective study of human immunodeficiency virus serostatus, human papillomavirus DNA, and cervical lesions detected by cytology and colposcopy. Infect. Dis. Obstet. Gynecol. 7, 158–164.CrossRefPubMedGoogle Scholar
- Ferrara, A., Nonn, M., Sehr, P., Schreckenberger, C., Pawlita, M., Durst, M., Schneider, A. and Kaufmann, A. M. (2003) Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients. J. Cancer Res. Clin. Oncol. 129, 521–530.CrossRefPubMedGoogle Scholar
- Guess, J. C. and McCance, D. J. (2005) Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3alpha production. J. Virol. 79, 14852–14862.CrossRefPubMedGoogle Scholar
- Hubert, P., Caberg, J. H., Gilles, C., Bousarghin, L., Franzen-Detrooz, E., Boniver, J. and Delvenne, P. (2005) E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions. J. Pathol. 206, 346–355.CrossRefPubMedGoogle Scholar
- Jimenez-Flores, R., Mendez-Cruz, R., Ojeda-Ortiz, J., Munoz-Molina, R., Balderas-Carrillo, O., de la Luz Diaz-Soberanes, M., Lebecque, S., Saeland, S., Daneri-Navarro, A., Garcia-Carranca, A., Ullrich, S. E. and Flores-Romo, L. (2006) High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans’ cells in the human female genital tract. Immunology 117, 220–228.CrossRefPubMedGoogle Scholar
- Matthews, K., Leong, C. M., Baxter, L., Inglis, E., Yun, K., Backstrom, B. T., Doorbar, J. and Hibma, M. (2003) Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin. J. Virol. 77, 8378–8385.CrossRefPubMedGoogle Scholar
- Santin, A. D., Bellone, S., Palmieri, M., Ravaggi, A., Romani, C., Tassi, R., Roman, J. J., Burnett, A., Pecorelli, S. and Cannon, M. J. (2006) HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecol. Oncol. 100, 469–478.CrossRefPubMedGoogle Scholar
- Walker, F., Adle-Biassette, H., Madelenat, P., Henin, D. and Lehy, T. (2005) Increased apoptosis in cervical intraepithelial neoplasia associated with HIV infection: implication of oncogenic human papillomavirus, caspases, and Langerhans cells. Clin. Cancer Res. 11, 2451–2458.CrossRefPubMedGoogle Scholar