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Author(s): Carlos Santos
Tiago Neto
Pedro Ferreirinha
Hugo Sousa
Joana Ribeiro
Margarida M. S. M. Bastos
Ana I. Faustino Rocha
Paula A. Oliveira
Rui Medeiros
Manuel Vilanova
Gil da Costa, R. M.
Title: Celecoxib promotes degranulation of CD8(+) T cells in HPV-induced lesions of K14-HPV16 transgenic mice
Issue Date: 2016-07-15
Abstract: 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.
Related Information: info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/Projetos Estratégicos/UID/EQU/00511/2013 - POCI-01-0145-FEDER-006939/Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia/LEPABE
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FEUP - Artigo em Revista Científica Internacional
ICBAS - Artigo em Revista Científica Internacional

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