Identification of Pancreatic Cancer-Associated Tumor Antigen from HSP-Enriched Tumor Lysate-Pulsed Human Dendritic Cells
Yonsei Medical Journal
;
: 1014-1027, 2014.
Artículo
en Inglés
| WPRIM
| ID: wpr-113973
ABSTRACT
PURPOSE:
Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunity are the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunity than DCs pulsed with conventional tumor lysate (TL), the underlying molecular mechanism is unclear. In order to explore the molecular basis of this approach and to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derived from TL- and HTL-pulsed dendritic cells by mass spectrophotometry. MATERIALS ANDMETHODS:
Human monocyte-derived dendritic cells were pulsed with TL or HTL prior to maturation induction. To delineate differences of MHC-bound peptide repertoire eluted from DCs pulsed with TL or HTL, nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS) was employed.RESULTS:
HTL, but not TL, significantly induced DC function, assessed by phenotypic maturation, allostimulation capacity and IFN-gamma secretion by stimulated allogeneic T cells. DCs pulsed with TL or HTL displayed pancreas or pancreatic cancer-related peptides in context of MHC class I and II molecules. Some of the identified peptides had not been previously reported as expressed in pancreatic cancer or cancer of other tissue types.CONCLUSION:
Our partial lists of MHC-associated peptides revealed the differences between peptide profiles eluted from HTL-and TL-loaded DCs, implying that induced heat shock proteins in HTL chaperone tumor-derived peptides enhanced their delivery to DCs and promoted cross-presentation by DC. These findings may aid in identifying novel tumor antigens or biomarkers and in designing future vaccination strategies.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Neoplasias Pancreáticas
/
Células Dendríticas
/
Línea Celular Tumoral
/
Antígenos de Neoplasias
Tipo de estudio:
Estudio diagnóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Yonsei Medical Journal
Año:
2014
Tipo del documento:
Artículo
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