title: Adoptive immunotherapy with Cl-IB-MECA-treated CD8+ T cells reduces melanoma growth in mice.
abstract: Cl-IB-MECA is a selective A3 adenosine receptor agonist, which plays a crucial role in limiting tumor progression. In mice, Cl-IB-MECA administration enhances the anti-tumor T cell-mediated response. However, little is known about the activity of Cl-IB-MECA on CD8+ T cells. The aim of this study was to investigate the effect of ex vivo Cl-IB-MECA treatment of CD8+ T cells, adoptively transferred in melanoma-bearing mice. Adoptive transfer of Cl-IB-MECA-treated CD8+ T cells or a single administration of Cl-IB-MECA (20 ng/mouse) inhibited tumor growth compared with the control group and significantly improved mouse survival. This was associated with the release of Th1-type cytokines and a greater influx of mature Langerin+ dendritic cells (LCs) into the tumor microenvironment. CD8+ T cells treated with Cl-IB-MECA released TNF-α which plays a critical role in the therapeutic efficacy of these cells when injected to mice. Indeed, neutralization of TNF-α by a specific monoclonal Ab significantly blocked the anti-tumor activity of Cl-IB-MECA-treated T cells. This was due to the reduction in levels of cytotoxic cytokines and the presence of fewer LCs. In conclusion, these studies reveal that ex vivo treatment with Cl-IB-MECA improves CD8+ T cell adoptive immunotherapy for melanoma in a TNF-α-dependent manner.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Salerno, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Montinaro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Forte
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D058909:Adenosine A3 Receptor Agonists; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide