HPV 유래의 자궁경부암에 대한 점막면역유도에서 IL-7의 역할에 대한 연구

Abstract

The induction of tissue-localized virus-specific CD8 T cell response is essential in the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. While the role of interleukin-7 (IL-7) has been studied for lymphocyte development in the lymphatic system, its immunological role in mucosal tissues is not well known. Here, we demonstrate that intravaginal treatment of Fc-fused interleukin-7 (IL-7-Fc), but not native IL-7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFN-γ, TNF-α, IL-6, and IL-1β), and anadhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes including CD4, CD8, γδ T cells, and dendritic cells (DCs). Importantly, topical administration of IL-7-Fc after intramuscular human papillomavirus (HPV) DNA vaccination increases the number of HPV-specific CD8 T cell in the genital mucosa, but not in the spleen, leading to a much stronger anti-tumor activity than the HPV DNA vaccine alone in an orthotopic murine cervical cancer model. Thus, these findings provide an important insight into the immunomodulatory role of IL-7-Fc via topical application and the design of a therapeutic vaccine regimen that induces an effective genital-mucosal CD8 T cell response.