000165948 001__ 165948
000165948 005__ 20260116150736.0
000165948 0247_ $$2doi$$a10.4161/21624011.2014.948705
000165948 0248_ $$2sideral$$a85747
000165948 037__ $$aART-2014-85747
000165948 041__ $$aeng
000165948 100__ $$aComet, NR
000165948 245__ $$aIFN-a signaling through PKC-Thetha is essential for anti-tumoral NK cell function
000165948 260__ $$c2014
000165948 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165948 5203_ $$aWe have previously shown that the development of a major histocompatibility complex class I (MHC-I)-deficient tumor was favored in protein kinase C-θ knockout (PKC-θ−/−) mice compared to that occurring in wild-type mice. This phenomenon was associated with scarce recruitment of natural killer (NK) cells to the tumor site, as well as impaired NK cell activation and reduced cytotoxicity ex vivo. Poly-inosinic:cytidylic acid (poly I:C) treatment activated PKC-θ in NK cells depending on the presence of a soluble factor produced by a different splenocyte subset. In the present work, we sought to analyze whether interleukin-15 (IL-15) and/or interferon-α (IFNα) mediate PKC-θ-dependent antitumor NK cell function. We found that IL-15 improves NK cell viability, granzyme B expression, degranulation capacity and interferon-γ (IFNγ) secretion independently of PKC-θ. In contrast, we found that IFNα improves the degranulation capability of NK cells against target cancer cells in a PKC-θ-dependent fashion both ex vivo and in vivo. Furthermore, IFNα induces PKC-θ auto-phosphorylation in NK cells, in a signal transduction pathway involving both phosphatidylinositol-3-kinase (PI3K) and phospholipase-C (PLC) activation. PKC-θ dependence was further implicated in IFNα-induced transcriptional upregulation of chemokine (C-X-C motif) ligand 10 (CXCL10), a signal transducer and activator of transcription-1 (STAT-1)-dependent target of IFNα. The absence of PKC-θ did not affect IFNα-induced STAT-1 Tyr701 phosphorylation but affected the increase in STAT-1 phosphorylation on Ser727, attenuating CXCL10 secretion. This connection between IFNα and PKC-θ in NK cells may be exploited in NK cell-based tumor immunotherapy.
000165948 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000165948 590__ $$a6.266$$b2014
000165948 591__ $$aONCOLOGY$$b21 / 209 = 0.1$$c2014$$dQ1$$eT1
000165948 591__ $$aIMMUNOLOGY$$b16 / 147 = 0.109$$c2014$$dQ1$$eT1
000165948 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000165948 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, JI$$uUniversidad de Zaragoza
000165948 700__ $$aRathore, MG
000165948 700__ $$aCatalán, E
000165948 700__ $$aGaraude, J
000165948 700__ $$aUze, G
000165948 700__ $$0(orcid)0000-0003-2156-8378$$aNaval, J$$uUniversidad de Zaragoza
000165948 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J$$uUniversidad de Zaragoza
000165948 700__ $$aVillalba, M
000165948 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A$$uUniversidad de Zaragoza
000165948 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000165948 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000165948 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000165948 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000165948 773__ $$g3, 8 (2014), e948705 [11 pp]$$pOncoimmunology$$tOncoImmunology$$x2162-4011
000165948 8564_ $$s17720977$$uhttps://zaguan.unizar.es/record/165948/files/texto_completo.pdf$$yPostprint
000165948 8564_ $$s1718880$$uhttps://zaguan.unizar.es/record/165948/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000165948 909CO $$ooai:zaguan.unizar.es:165948$$particulos$$pdriver
000165948 951__ $$a2026-01-16-15:06:17
000165948 980__ $$aARTICLE