Celecoxib promotes degranulation of CD8(+) T cells in HPV-induced lesions of K14-HPV16 transgenic mice

• Type: Article in International Scientific Journal
• Date: 2016-07-15

Authors

Carlos Santos (Author) ICBAS; Tiago Neto (Author) ICBAS; Pedro Ferreirinha (Author) ICBAS; Hugo Sousa (Author) Other; Joana Ribeiro (Author) Other; Margarida M. S. M. Bastos (Author) FEUP; Ana I. Faustino Rocha (Author) Other; Paula A. Oliveira (Author) Other; Rui Medeiros (Author) ICBAS; Manuel Vilanova (Author) ICBAS; Gil da Costa, R. M. (Author) FEUP

Journal

Title: Life Sciences

Vol. 157

Pages: 67-73

ISSN: 0024-3205

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 20 Citations

ISI Web of Science

Scopus - 24 Citations

Pubmed / Medline

Associated Projects

LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

Other information

Authenticus ID: P-00K-JKN

DOI: 10.1016/j.lfs.2016.05.040

Abstract (EN): Aims: Human papillomavirus (HPV) is a known biologic carcinogen which is commonly transmitted through sexual intercourse. CD8(+) T cells are known effectors against tumour cells and an important prognostic marker in HPV-induced cancers. COX-2 inhibitors enhance CD8(+) T cell activity against some cancers. In this work, we sought to study the presence and activation of CD8(+) T lymphocytes in lesions from K14-HPV16 transgenic mice and the immunomodulatory effect of celecoxib (CXB) over these cells. Main methods: Skin samples of CXB-treated and untreated HPV16(-/-) and HPV16(+/-) mice were enzymatically digested and analysed by flow cytometry to assess CD8+ and CD8(+) CD107a(+) T cell infiltrates. Matched skin samples were classified histologically. Key findings: HPV16(+/-) mice presented higher CD8(+) T cell infiltration than HPV16(-/-) animals (P < 0.001). Older HPV16(+/-) animals showed epidermal dysplasia and increased percentages of CD8+ CD107a(+) T cells compared with younger animals with hyperplasia (P < 0.001), validating this model for testing the effects of celecoxib on CD8(+) T cells. CXB-treated HPV16(+/-) mice showed higher percentages of CD8(+) CD107a(+) T cells compared with untreated HPV16(+/-) animals (P < 0.01), but no differences were observed concerning the progression of epidermal lesions. Significance: These findings indicate that celecoxib enhances the degranulation of CD8(+) T cells on HPV16-induced lesions, suggesting the potential clinical use of COX-2 inhibitors. Additionally, this study demonstrates the usefulness of the K14-HPV16 mouse model for testing therapeutic immunomodulatory approaches.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7