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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2014.1
- 수록면
- 1,014 - 1,027 (14page)
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Purpose: Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunityare the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunitythan DCs pulsed with conventional tumor lysate (TL), the underlying molecularmechanism is unclear. In order to explore the molecular basis of this approachand to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derivedfrom TL- and HTL-pulsed dendritic cells by mass spectrophotometry. Materialsand Methods: 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-γ 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 antigensor biomarkers and in designing future vaccination strategies.
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참고문헌 (22)
참고문헌 신청
Admon A / 2003 / Tumor antigens and proteomics from the point of view of the major histocompatibility complex peptides / Mol Cell Proteomics 2 : 388 ~ 398
Berger TG / 2002 / Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories / J Immunol Methods 268 : 131 ~ 140
Dolan BP / 2006 / Tumor-specific CD4+ T cells are activated by “cross-dressed” dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer va
Fields RC / 1998 / Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo / Proc Natl Acad Sci U S A 95 : 9482
Galea-Lauri J / 2004 / Strate
Berger TG / 2002 / Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories / J Immunol Methods 268 : 131 ~ 140
Dolan BP / 2006 / Tumor-specific CD4+ T cells are activated by “cross-dressed” dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer va
Fields RC / 1998 / Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo / Proc Natl Acad Sci U S A 95 : 9482
Galea-Lauri J / 2004 / Strate
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