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Role of GM-CSF signaling in cell-based tumor immunization

Zarei, Shohreh
Kopf, Manfred
Dranoff, Glenn
Published in Blood. 2009, vol. 113, no. 26, p. 6658-6668
Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cell-based vaccination in 2 tumor models. First, we vaccinated C57BL/6 mice lacking either GM-CSF, IL-5, or beta-common chain (betac), a receptor subunit essential for GM-CSF and IL-5 signaling, with melanoma cells engineered to produce GM-CSF. Tumor vaccination was effective in both GM-CSF(-/-) and IL-5(-/-) mice, showing that protective immunization is independent of both endogenous cytokines. However, all betac(-/-) animals developed tumor. Loss of tumor immunity in betac(-/-) mice does not reflect global impairment in cell-mediated immunity, as contact hypersensitivity reaction to haptens is unaltered. The importance of tumor cell-derived GM-CSF was highlighted by recruitment of dendritic cells at the vaccination site in wild-type, GM-CSF(-/-), and IL-5(-/-) but not in betac(-/-) mice. In the second model, vaccination with unmodified RENCA cells showed similar results with efficient immunization in BALB/c wild-type and GM-CSF(-/-), whereas all betac(-/-) animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through betac receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF-secreting tumor cells and a spontaneously immunogenic models.
Keywords AnimalsCancer Vaccines/*immunologyCarcinoma, Renal Cell/immunology/pathology/*prevention & controlCell Line, Tumor/secretion/transplantationCulture Media, Conditioned/chemistryCytokine Receptor Common beta Subunit/deficiency/genetics/*physiologyCytokines/analysisDendritic Cells/immunologyDermatitis, Contact/immunologyGranulocyte-Macrophage Colony-Stimulating Factor/deficiency/genetics/*physiologyInjections, SubcutaneousInterleukin-3/deficiency/genetics/physiologyInterleukin-5/deficiency/genetics/physiologyKidney Neoplasms/immunology/pathologyMelanoma, Experimental/immunology/pathology/*prevention & controlMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutRecombinant Fusion Proteins/physiologySpecies SpecificityVaccination/methods
PMID: 19282460
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Research groups Chirurgie viscérale (104)
Molécules d'adhésion et processus de migration cellulaire (167)
La recherche translationnelle en oncologie (654)
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ZAREI, Shohreh et al. Role of GM-CSF signaling in cell-based tumor immunization. In: Blood, 2009, vol. 113, n° 26, p. 6658-6668. https://archive-ouverte.unige.ch/unige:20188

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Deposited on : 2012-04-23

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