title: 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.affiliation: Department of Pharmaceutical Sciences, Biomedical Section, University of Salerno, Fisciano (SA), Italy. smorello@unisa.it
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Antonella
authors.initials: A
authors.lastname: Montinaro
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.forename: Anta
authors.initials: A
authors.lastname: Ngkelo
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
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide