TY - JOUR
T1 - Cervical cancer cells suppress effector functions of cytotoxic T cells through the adenosinergic pathway
AU - Mora-García, M. L.
AU - Ávila-Ibarra, L. R.
AU - García-Rocha, R.
AU - Weiss-Steider, B.
AU - Hernández-Montes, J.
AU - Don-López, C. A.
AU - Gutiérrez-Serrano, V.
AU - Titla-Vilchis, I. J.
AU - Fuentes-Castañeda, M. C.
AU - Monroy-Mora, A.
AU - Jave-Suárez, L. F.
AU - Chacón-Salinas, R.
AU - Vallejo-Castillo, L.
AU - Pérez-Tapia, S. M.
AU - Monroy-García, A.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10
Y1 - 2017/10
N2 - Background The expression of CD73 in tumor cells plays a significant role in the production of adenosine (Ado) that suppresses antitumor effector cells. Methods 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. Results 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 (>400 μM) compared to HPV-CeCa cells (<200 μM) in the presence of AMP, as well as a 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. Conclusion 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.
AB - Background The expression of CD73 in tumor cells plays a significant role in the production of adenosine (Ado) that suppresses antitumor effector cells. Methods 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. Results 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 (>400 μM) compared to HPV-CeCa cells (<200 μM) in the presence of AMP, as well as a 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. Conclusion 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.
KW - Adenosine
KW - CD73
KW - CTLs
KW - Cervical cancer cells
KW - Immunosuppression
UR - http://www.scopus.com/inward/record.url?scp=85029770195&partnerID=8YFLogxK
U2 - 10.1016/j.cellimm.2017.09.002
DO - 10.1016/j.cellimm.2017.09.002
M3 - Artículo
C2 - 28950987
AN - SCOPUS:85029770195
SN - 0008-8749
VL - 320
SP - 46
EP - 55
JO - Cellular Immunology
JF - Cellular Immunology
ER -