Abstract
The protein kinase C-θ (PKCθ), which is essential for T cell function and survival, is also required for efficient anti-tumor immune surveillance. Natural killer (NK) cells, which express PKCθ, play a prominent role in this process, mainly by elimination of tumor cells with reduced or absent major histocompatibility complex class-I (MHC-I) expression. This justifies the increased interest of the use of activated NK cells in anti-tumor immunotherapy in the clinic. The in vivo development of MHC-I-deficient tumors is much favored in PKCθ−/− mice compared with wild-type mice. Recent data offer some clues on the mechanism that could explain the important role of PKCθ in NK cell-mediated anti-tumor immune surveillance: some studies show that PKCθ is implicated in signal transduction and anti-tumoral activity of NK cells elicited by interleukin (IL)-12 or IL-15, while others show that it is implicated in NK cell functional activation mediated by certain killer-activating receptors. Alternatively, the possibility that PKCθ is involved in NK cell degranulation is discussed, since recent data indicate that it is implicated in microtubule-organizing center polarization to the immune synapse in CD4+ T cells. The implication of PKC isoforms in degranulation has been more extensively studied in cytotoxic T lymphocyte, and these studies will be also summarized.
Highlights
PKCθ IN T CELLS The protein kinase C-θ (PKC-θ) was initially isolated as a PKC isoform expressed in T cells (Baier et al, 1993), it was demonstrated afterward that its expression was not restricted to them (Isakov and Altman, 2002)
IL-15 is able to signal through PKCθ, this signaling is not needed for the main functional effects of IL-15 on natural killer (NK) cells (Aguiló et al, in preparation)
In the case of cytotoxic T lymphocytes (CTLs)-mediated tumor control, this can be explained by its role as a CTL survival factor (Barouch-Bentov et al, 2005), the impaired cytokine response observed in PKCθ deficient animals (Sun et al, 2000) and its implication in Fas Ligand (FasL) expression (Villalba et al, 1999; Villunger et al, 1999; Pardo et al, 2003)
Summary
PKCθ IN T CELLS The protein kinase C-θ (PKC-θ) was initially isolated as a PKC isoform expressed in T cells (Baier et al, 1993), it was demonstrated afterward that its expression was not restricted to them (Isakov and Altman, 2002). In this study no effect of PKCθ deficiency was either observed on cytotoxicity against YAC-1 cells or against tumoral cells over-expressing KAR ligands (Tassi et al, 2008).
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