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

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.

• Authors: Silvana Morello, Rosalinda Sorrentino, Antonella Montinaro, Antonio Luciano, Piera Maiolino, Anta Ngkelo, Claudio Arra, Ian M Adcock, Aldo Pinto
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 13 Issue 4 Pg. 365-73 (Apr 2011) ISSN: 1476-5586 [Electronic] United States
• PMID: 21472141 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Adenosine
• 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide

Topics

• Adenosine (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• CD8-Positive T-Lymphocytes (metabolism, physiology)
• Cell Line, Tumor
• Chemotaxis, Leukocyte (drug effects)
• Female
• Immunity, Cellular (drug effects, physiology)
• Killer Cells, Natural (metabolism, physiology)
• Lymphocyte Activation (drug effects)
• Melanoma, Experimental (drug therapy, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Skin Neoplasms (drug therapy, immunology, pathology)
• Tumor Microenvironment (drug effects)