Mora-García M L, Ávila-Ibarra L R, García-Rocha R, Weiss-Steider B, Hernández-Montes J, Don-López C A, Gutiérrez-Serrano V, Titla-Vilchis I J, Fuentes-Castañeda M C, Monroy-Mora A, Jave-Suárez L F, Chacón-Salinas R, Vallejo-Castillo L, Pérez-Tapia S M, Monroy-García A
Laboratorio de Inmunobiología, Unidad de Diferenciación Celular y Cáncer, FES-Zaragoza, UNAM, Ciudad de México, Mexico.
Laboratorio de Inmunología y Cáncer, Unidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, Mexico.
Cell Immunol. 2017 Oct;320:46-55. doi: 10.1016/j.cellimm.2017.09.002. Epub 2017 Sep 7.
The expression of CD73 in tumor cells plays a significant role in the production of adenosine (Ado) that suppresses antitumor effector cells.
In this study we analyzed the capability of HPV-positive (HPV+) cervical cancer (CeCa) cell lines CaSki, SiHa, HeLa, and RoVa; and HPV-negative (HPV-) cell lines C33A and ViBo to produce Ado and inhibit effector functions of CD8+ T cells.
HPV+ CeCa cells expressed significantly higher levels of CD73 in the membrane (p<0.01) than HPV- CeCa cells and this expression was associated with the production of larger amounts of Ado (>400μM) compared to HPV-CeCa cells (<200μM) in the presence of AMP, as well asa stronger inhibition of (>50%) proliferation, activation, and cytotoxic activity of CD8+ T cells via interaction with A2A adenosine receptor. We also provide evidence that silenced E6/E7 expression in CeCa cells, strongly reduced its CD73 expression level and its capability to generate Ado.
This results suggest that HPV infection, which is associated with more than 99% of CeCa cases, may present an increased constitutive expression of CD73 in cervical neoplasia to contribute to the suppression of the immune response mediated by the production of large amounts of Ado.
肿瘤细胞中CD73的表达在抑制抗肿瘤效应细胞的腺苷（Ado）产生中起重要作用。
在本研究中，我们分析了人乳头瘤病毒阳性（HPV+）的宫颈癌（CeCa）细胞系CaSki、SiHa、HeLa和RoVa，以及人乳头瘤病毒阴性（HPV-）细胞系C33A和ViBo产生Ado以及抑制CD8+T细胞效应功能的能力。
HPV+的CeCa细胞在细胞膜上表达的CD73水平显著高于HPV-的CeCa细胞（p<0.01），并且在存在AMP的情况下，与HPV-的CeCa细胞（<200μM）相比，这种表达与产生大量Ado（>400μM）相关，同时通过与A2A腺苷受体相互作用对CD8+T细胞的增殖、激活和细胞毒性活性的抑制作用更强（>50%）。我们还提供证据表明，CeCa细胞中E6/E7表达沉默会强烈降低其CD73表达水平及其产生Ado的能力。
这些结果表明，与超过99%的CeCa病例相关的HPV感染，可能在宫颈肿瘤形成过程中导致CD73组成性表达增加，从而通过产生大量Ado来抑制免疫反应。
