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01.04.2009 | Original Article

NK1.1⁺ cells mediate the antitumor effects of a dual Toll-like receptor 7/8 agonist in the disseminated B16-F10 melanoma model

verfasst von: Calin D. Dumitru, Mary A. Antonysamy, Kevin S. Gorski, Dave D. Johnson, Laxma G. Reddy, Jody L. Lutterman, Melissa M. Piri, Joel Proksch, Sean M. McGurran, Elaine A. Egging, Felicia R. Cochran, Kenneth E. Lipson, Mark A. Tomai, Gary W. Gullikson

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 4/2009

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Abstract

Innate immune stimulation with Toll-like receptor (TLR) agonists is a proposed modality for immunotherapy of melanoma. Here, a TLR7/8 agonist, 3M-011, was used effectively as a single systemic agent against disseminated mouse B16-F10 melanoma. The investigation of the mechanism of antitumor action revealed that the agonist had no direct cytotoxic effects on tumor cells tested in vitro. In addition, 3M-011 retained its effectiveness in scid/B6 mice and scid/NOD mice, eliminating the requirement for T and B cells, but lost its activity in beige (bg/bg) and NK1.1-immunodepleted mice, suggesting a critical role for natural killer (NK) cells in the antitumor response. NK cytotoxicity was enhanced in vivo by the TLR7/8 agonist; this activation was long lasting, as determined by sustained expression of the activation marker CD69. Also, in human in vitro studies, 3M-011 potentiated NK cytotoxicity. TLR7/8-mediated NK-dependent antitumor activity was retained in IFN-α/β receptor-deficient as well as perforin-deficient mice, while depletion of IFN-γ significantly decreased the ability of 3M-011 to delay tumor growth. Thus, IFN-γ-dependent functions of NK cell populations appear essential for cancer immunotherapy with TLR7/8 agonists.

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Titel: NK1.1+ cells mediate the antitumor effects of a dual Toll-like receptor 7/8 agonist in the disseminated B16-F10 melanoma model
verfasst von: Calin D. Dumitru
Mary A. Antonysamy
Kevin S. Gorski
Dave D. Johnson
Laxma G. Reddy
Jody L. Lutterman
Melissa M. Piri
Joel Proksch
Sean M. McGurran
Elaine A. Egging
Felicia R. Cochran
Kenneth E. Lipson
Mark A. Tomai
Gary W. Gullikson
Publikationsdatum: 01.04.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0581-7

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17.04.2024 | Mammakarzinom | Nachrichten

Springer Medizin

NK1.1⁺ cells mediate the antitumor effects of a dual Toll-like receptor 7/8 agonist in the disseminated B16-F10 melanoma model

Abstract

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Abstract

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