Abstract

There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs by epitopes and NK interactions for cytotoxicity in tumors. In this study, DC cells activated by the HPV16E7.49-57 epitope and LPS were co-cultured with NK cells in vitro, and then used ot immunize mice to study CTL activity of TC-1, which constitutively expresses HPV16E6E7, with an LDH release assay. Cytotoxicity in mice immunized with DC loaded with epitope HPVE7.49-57 vaccine co-cultured with NK was enhanced significantly (p<0.01). In conclusion, talk-across between DC and NK cells enhances their functions, also improving cytotoxicity againsttumor cells, suggesting that activated DC-NK by epitopes has potential application for cancer-specific immuno-cellular therapy.

Highlights

  • Cervical cancer is currently the only one gynecologic malignancy with definite cause, and reported to be related with persistent infection due to high-risk human papillomavirus

  • Identification of dendritic cell (DC) and natural killer (NK) cells Cultured DC and NK cells were analyzed by ordinary optical microscopy and FACS (Figure 1, 2)

  • DC cells interact with a number of effector cells such as T cells, macrophages and NK cell in vivo after vaccination (Degli-Esposti et al, 2005; Shanker et al, 2007; Bellora et al, 2010; Eissmann et al, 2010; Shanker, 2010; Shanker et al, 2010)

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Summary

Introduction

Cervical cancer is currently the only one gynecologic malignancy with definite cause, and reported to be related with persistent infection due to high-risk human papillomavirus All of these treatments have certain effect on cervical cancer but accompanying side effects, recurrence and metastasis. The current available commercialized cervical cancer vaccine has been proved to have no therapeutic effect on patients infected with HPV or cervical cancer patients. It is still necessary to explore new treatment for HPV infection or cervical cancer, among which the immune cell therapy that has been proved to be functional for cancer treatment in recent years has been gaining more attention. Recent clinical trials have shown that the clinical results are more related with NK (Natural killer) response after DCs or DC derived-exosomes inoculation than T-cell responses (Osada et al, 2006; Di Nicola et al, 2009; Viaud et al, 2009)

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