Decreased invariant natural killer T-cell-mediated antitumor immune response in patients with gastric cancer
Author
dc.contributor.author
Ascui, Gabriel
Author
dc.contributor.author
Gálvez Jirón, Felipe
Author
dc.contributor.author
Kramm, Karina
Author
dc.contributor.author
Schafer, Carolina
Author
dc.contributor.author
Siña, Josefina
Author
dc.contributor.author
Pola, Víctor
Author
dc.contributor.author
Cristi, Francisca
Author
dc.contributor.author
Hernández, Carolina
Author
dc.contributor.author
Garrido Tapia, Macarena
Author
dc.contributor.author
Pesce Reyes, Bárbara
Author
dc.contributor.author
Bustamante Zamorano, Marco
Author
dc.contributor.author
Fluxá Rojas, Paula
Author
dc.contributor.author
Molina Sampayo, María Carmen
Author
dc.contributor.author
Ribeiro, Carolina H.
Admission date
dc.date.accessioned
2020-06-03T15:15:35Z
Available date
dc.date.available
2020-06-03T15:15:35Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Immunology & Cell Biology 2020; 1–14
es_ES
Identifier
dc.identifier.other
10.1111/imcb.12331
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/175184
Abstract
dc.description.abstract
Gastric 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.
es_ES
Patrocinador
dc.description.sponsorship
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
11110456
1130330
University of Chile
ENLACE-VID ENL012/15
Biomedical Sciences Institute (ICBM) Funding Grant 2018
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
FONDEQUIP140032
AIC-08
ICBM, School of Medicine of University of Chile, Santiago, Chile