Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression.
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.
Aguiló
Juan I
JI
Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain.
Garaude
Johan
J
Pardo
Julián
J
Villalba
Martín
M
Anel
Alberto
A
D000818:Animals; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology*; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D000074121:Protein Kinase C-theta; D019139:Tumor Escape / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta