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

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• 作者：Carlos Santos^a ; ^{carlos.e.santos792@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Tiago Neto^a ; ^b ; ^c ; Pedro Ferreirinha^a ; Hugo Sousa^b ; ^d ; Joana Ribeiro^b ; ^d ; ^e ; Margarida M.S.M. Bastos^f ; Ana I. Faustino-Rocha^c ; Paula A. Oliveira^c ; ^g ; Rui Medeiros^a ; ^b ; ^d ; ^e ; ^h ; Manuel Vilanova^a ; Rui M. Gil da Costa^b ; ^f
• 关键词：CD8+ T lymphocytes ; Celecoxib ; COX-2 inhibition ; Human papillomavirus ; K14-HPV16 transgenic mice
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：157
• 期：Complete
• 页码：67-73
• 全文大小：810 K

文摘

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.