Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice

Antonella Montinaro, Giovanni Forte, Rosalinda Sorrentino, Antonio Luciano, Giuseppe Palma, Claudio Arra, Ian M. Adcock, Aldo Pinto, Silvana Morello

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere45401
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 24 2012

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Adoptive Immunotherapy
T-cells
immunotherapy
melanoma
Melanoma
T-lymphocytes
T-Lymphocytes
mice
Growth
Tumors
neoplasms
dendritic cells
cytokines
Dendritic Cells
Adenosine A3 Receptor Agonists
Neoplasms
Bearings (structural)
Cytokines
adenosine
N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Montinaro, A., Forte, G., Sorrentino, R., Luciano, A., Palma, G., Arra, C., ... Morello, S. (2012). Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice. PLoS One, 7(9), [e45401]. https://doi.org/10.1371/journal.pone.0045401

Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice. / Montinaro, Antonella; Forte, Giovanni; Sorrentino, Rosalinda; Luciano, Antonio; Palma, Giuseppe; Arra, Claudio; Adcock, Ian M.; Pinto, Aldo; Morello, Silvana.

In: PLoS One, Vol. 7, No. 9, e45401, 24.09.2012.

Research output: Contribution to journalArticle

Montinaro, A, Forte, G, Sorrentino, R, Luciano, A, Palma, G, Arra, C, Adcock, IM, Pinto, A & Morello, S 2012, 'Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice', PLoS One, vol. 7, no. 9, e45401. https://doi.org/10.1371/journal.pone.0045401
Montinaro, Antonella ; Forte, Giovanni ; Sorrentino, Rosalinda ; Luciano, Antonio ; Palma, Giuseppe ; Arra, Claudio ; Adcock, Ian M. ; Pinto, Aldo ; Morello, Silvana. / Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice. In: PLoS One. 2012 ; Vol. 7, No. 9.
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