dc.creatorAscui, Gabriel
dc.creatorGálvez Jirón, Felipe
dc.creatorKramm, Karina
dc.creatorSchafer, Carolina
dc.creatorSiña, Josefina
dc.creatorPola, Víctor
dc.creatorCristi, Francisca
dc.creatorHernández, Carolina
dc.creatorGarrido Tapia, Macarena
dc.creatorPesce Reyes, Bárbara
dc.creatorBustamante Zamorano, Marco
dc.creatorFluxá Rojas, Paula
dc.creatorMolina Sampayo, María Carmen
dc.creatorRibeiro, Carolina H.
dc.date.accessioned2020-06-03T15:15:35Z
dc.date.available2020-06-03T15:15:35Z
dc.date.created2020-06-03T15:15:35Z
dc.date.issued2020
dc.identifierImmunology & Cell Biology 2020; 1–14
dc.identifier10.1111/imcb.12331
dc.identifierhttps://repositorio.uchile.cl/handle/2250/175184
dc.description.abstractGastric cancer (GC) is the third most common cause of cancer-related death worldwide. Invariant natural killer T (iNKT) cells are innate-like cytotoxic T lymphocytes involved in tumor immune surveillance. They can be activated either through CD1d-presented glycolipid antigens recognized by their invariant T-cell receptor, cytokines or by sensing tumor-associated stress-induced ligands through the natural killer group 2, member D (NKG2D) receptor. Although the number and functionality of iNKT cells may be decreased in several types of cancer, here we show that GC patients presented a mild increase in iNKT cell frequencies and numbers in the blood compared with healthy donors. In GC patients, iNKT cells, expanded in vitro with alpha-galactosyl ceramide and stimulated with phorbol 12-myristate 13-acetate and ionomycin, produced higher levels of interleukin-2 and transforming growth factor-beta, while their capacity to degranulate remained preserved. Because tumor-derived epithelial cell adhesion molecule-positive epithelial cells did not display surface CD1d, and NKG2D ligands (NKG2DLs) were detected in the gastric tumor milieu, we envisioned a role for NKG2D in iNKT cell functions. Peripheral iNKT cells from GC patients and controls presented similar levels of NKG2D; nevertheless, the percentages of interferon-gamma-producing and CD107a-positive iNKT cells from patients were reduced upon challenge with CD1d-negative, NKG2DL-positive K562 cells, suggesting a compromised response by iNKT cells in GC patients, which may not result from impaired NKG2D/NKG2DL signaling. The decreased response of iNKT cells may explain the fact that higher frequencies of circulating iNKT cells did not confer a survival benefit for GC patients. Therefore, functional impairment of iNKT cells in GC may contribute to tumor immune escape and favor disease progression.
dc.languageen
dc.publisherWiley
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceImmunology & Cell Biology
dc.subjectCD1d
dc.subjectCytotoxicity
dc.subjectGastric cancer
dc.subjectINKT cells
dc.subjectNKG2D receptor
dc.titleDecreased invariant natural killer T-cell-mediated antitumor immune response in patients with gastric cancer
dc.typeArtículo de revista


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