Document Detail


TAP expression level in tumor cells defines the nature and processing of MHC class I peptides for recognition by tumor-specific cytotoxic T lymphocytes.
MedLine Citation:
PMID:  23302073     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We identified that the antigen preprocalcitonin (ppCT) is recognized on a human lung carcinoma by a cytotoxic T lymphocyte clone derived from autologous tumor-infiltrating lymphocytes. The antigenic peptide ppCT(16-25) is encoded by the gene calcitonin-related polypeptide alpha (CALCA), which codes for CT and is overexpressed in several lung carcinomas compared with normal tissues. The ppCT peptide is derived from the C-terminal region of the signal peptide and is processed independently of proteasomes and the transporter associated with antigen processing (TAP)1/TAP2 heterodimeric complexes. Instead, processing occurs within the endoplasmic reticulum by a novel mechanism involving signal pepsidase (SP) and signal peptide peptidase (SPP). Although lung cancer cells bearing the ppCT(16-25) epitope displayed low levels of TAP, restoration of TAP expression by interferon (IFN)-γ treatment or by TAP1/TAP2 gene transfer inhibited ppCT antigen presentation. Thus, the ppCT(16-25) human tumor epitope requires low TAP expression for efficient presentation. These results indicate that emerging SP-generated peptides represent alternative T cell targets that permit cytotoxic T lymphocytes to destroy TAP-impaired tumors, a process that helps to overcome tumor escape from CD8(+) T cell immunity. Additionally, our data suggest that ppCT is a promising candidate for cancer immunotherapy.
Authors:
Faten El Hage; Aurélie Durgeau; Fathia Mami-Chouaib
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  -     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 New York Academy of Sciences.
Affiliation:
Chimie et Sciences de la Vie et de la Terre, Université Saint-Esprit de Kaslik, Jounieh, Lebanon. Integrated Research Cancer Institute in Villejuif, Institut de Cancérologie Gustave Roussy, Villejuif, France.
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