Decreased invariant natural killer T-cell-mediated antitumor immune response in patients with gastric cancer
| Autor: | Karina Kramm, Marco Bustamante, Carolina H. Ribeiro, Carolina Schäfer, Felipe Gálvez-Jirón, Macarena Garrido-Tapia, Gabriel Ascui, Carolina Hernández, Josefina Siña, Paula Fluxá, Francisca Cristi, Víctor Pola, María Carmen Molina, Barbara Pesce |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Immunology Cell Receptors Antigen T-Cell chemical and pharmacologic phenomena Lymphocyte Activation 03 medical and health sciences 0302 clinical medicine Immune system Antigen Stomach Neoplasms medicine Immunology and Allergy Cytotoxic T cell Humans Receptor biology Chemistry Cell Biology NKG2D 030104 developmental biology medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K CD1D biology.protein Cancer research Cytokines Natural Killer T-Cells Antigens CD1d K562 Cells 030215 immunology K562 cells |
| Zdroj: | Immunology and cell biologyReferences. 98(6) |
| ISSN: | 1440-1711 |
| Popis: | 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 α-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-γ-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. |
| Databáze: | OpenAIRE |
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