Cervical cancer cells suppress effector functions of cytotoxic T cells through the adenosinergic pathway
| Autor: | L.R. Ávila-Ibarra, Benny Weiss-Steider, Rosario García-Rocha, Luis Felipe Jave-Suárez, Jorge Hernández-Montes, María de Lourdes Mora-García, Sonia Mayra Pérez-Tapia, Rommel Chacón-Salinas, Alberto Monroy-García, A. Monroy-Mora, M.C. Fuentes-Castañeda, Christian Azucena Don-López, I.J. Titla-Vilchis, Vianey Gutiérrez-Serrano, Luis Vallejo-Castillo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Adenosine Receptor Adenosine A2A Papillomavirus E7 Proteins Immunology Uterine Cervical Neoplasms Adenosinergic Biology GPI-Linked Proteins 03 medical and health sciences 0302 clinical medicine Immune system Cell Line Tumor Cytotoxic T cell Humans RNA Small Interfering 5'-Nucleotidase Papillomaviridae Immunosuppression Therapy Lymphokine-activated killer cell Effector Papillomavirus Infections Oncogene Proteins Viral Adenosine Monophosphate DNA-Binding Proteins Repressor Proteins 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research Interleukin 12 Female Tumor Escape CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Cellular immunology. 320 |
| ISSN: | 1090-2163 |
| Popis: | 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 (p0.01) 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. |
| Databáze: | OpenAIRE |
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