Document Detail


Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases.
MedLine Citation:
PMID:  23319306     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Studies in preclinical models have demonstrated the superior anti-tumor effect of CpGoligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ, and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice.Treatment with aerosolizedCpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas onlyi.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, since mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicatethat tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy. © 2013 Wiley Periodicals, Inc.
Authors:
Lucia Sfondrini; Michele Sommariva; Monica Tortoreto; Alessandra Meini; Silvia Piconese; Marco Calvaruso; Nick Van Rooijen; Raffaella Bonecchi; Nadia Zaffaroni; Mario P Colombo; Elda Tagliabue; Andrea Balsari
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 UICC.
Affiliation:
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan (Italy). lucia.sfondrini@unimi.it.
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