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Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression

Abstract : Protein kinase C-theta (PKCtheta) was initially isolated as an important PKC isoform expressed in T cells, although its expression is not restricted to these cells. Despite the central function of PKCtheta in several immune responses, its role in the antitumor response against MHC class I (MHC-I)-negative cells has not been investigated. This is an important issue because most tumor cells growing in vivo down-regulate MHC-I expression to escape the CTL-mediated response. In the present work, we show that in vivo development of a MHC-I-deficient tumor (RMA-S) is much favored in PKCtheta(-/-) mice compared with wild-type mice. This is associated with a reduced recruitment of NK cells to the site of tumor development and a reduced activation status of recruited NK cells. This correlates with a reduced ex vivo and in vivo cytotoxic potential of NK cells isolated from PKCtheta(-/-) mice treated with polyinosinic:polycytidylic acid. Consistently, polinosinic:cytidilic acid treatment induces PKCtheta expression and activation of its enzymatic activity in NK cells in an indirect manner. These observations underline the relevance of PKCtheta as a key molecule in NK cell-mediated antitumor immune surveillance.
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Submitted on : Thursday, July 25, 2019 - 11:10:30 AM
Last modification on : Friday, June 12, 2020 - 1:23:21 PM

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J. I. Aguilo, J. Garaude, Juan Carlos Pardo, M. Villalba, A. Anel. Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 182 (4), pp.1972--81. ⟨10.4049/jimmunol.0801820⟩. ⟨hal-02194087⟩



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