NK1.1 + cells and CD8 + T cells mediate the antitumor activity of CL-IB-MECA in a mouse melanoma model

Silvana Morello, Rosalinda Sorrentino, Antonella Montinaro, Antonio Luciano, Piera Maiolino, Anta Ngkelo, Claudio Arra, Ian M. Adcock, Aldo Pinto

Research output: Contribution to journalArticle

Abstract

Cl-IB-MECA, synthetic A 3 adenosine receptor agonist, is a potential anticancer agent. In this study, we have examined the effect of Cl-IB-MECA in a mouse melanoma model. Cl-IB-MECA significantly inhibited tumor growth in immune-competent mice. Notably, the number of tumor-infiltrating NK1.1 + cells and CD8 + T cells was significantly increased in Cl-IB-MECA-treated mice. This effect was correlated with high levels of tumor necrosis factor α (TNF-α) and interferon γ in melanoma tissue. Depletion of either CD8 + T cells or NK1.1 + cells completely abrogated the antitumor effect of Cl-IB-MECA. Accordingly, Cl-IB-MECA did not affect tumor growth in nude mice. In addition, we also found that the number of mature and active conventional dendritic cells at the tumor site was increased after Cl-IB-MECA administration. Moreover, Cl-IB-MECA significantly increased TNF-α and IL-12p40 release from splenic CD11c + cells. In conclusion, our study provides novel insights into the mechanism by which Cl-IB-MECA leads to an effective antitumor response that involves the activation of natural killer cells and CD8 + T cells and further highlights its therapeutic potential.

Original languageEnglish
Pages (from-to)365-373
Number of pages9
JournalNeoplasia (United States)
Volume13
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Melanoma
T-Lymphocytes
Neoplasms
Tumor Necrosis Factor-alpha
Purinergic P1 Receptor Agonists
Interleukin-12 Subunit p40
N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
Growth
Nude Mice
Natural Killer Cells
Antineoplastic Agents
Dendritic Cells
Interferons

ASJC Scopus subject areas

  • Cancer Research

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NK1.1 + cells and CD8 + T cells mediate the antitumor activity of CL-IB-MECA in a mouse melanoma model. / Morello, Silvana; Sorrentino, Rosalinda; Montinaro, Antonella; Luciano, Antonio; Maiolino, Piera; Ngkelo, Anta; Arra, Claudio; Adcock, Ian M.; Pinto, Aldo.

In: Neoplasia (United States), Vol. 13, No. 4, 04.2011, p. 365-373.

Research output: Contribution to journalArticle

Morello, Silvana ; Sorrentino, Rosalinda ; Montinaro, Antonella ; Luciano, Antonio ; Maiolino, Piera ; Ngkelo, Anta ; Arra, Claudio ; Adcock, Ian M. ; Pinto, Aldo. / NK1.1 + cells and CD8 + T cells mediate the antitumor activity of CL-IB-MECA in a mouse melanoma model. In: Neoplasia (United States). 2011 ; Vol. 13, No. 4. pp. 365-373.
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