| Autor: |
Vikman, Sofia, Giandomenico, Valeria, Sommaggio, Roberta, Öberg, Kjell, Essand, Magnus, Tötterman, Thomas |
| Předmět: |
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| Zdroj: |
Cancer Immunology, Immunotherapy; Mar2008, Vol. 57 Issue 3, p399-409, 11p, 3 Charts, 5 Graphs |
| Abstrakt: |
The aim of the study was to identify immunogenic HLA-A*0201-binding epitopes derived from a number of classical midgut carcinoid-associated proteins. CD8+ T cells recognizing tumor-associated antigen (TAA) epitopes are of great interest for the establishment of immunotherapy as a novel treatment for this type of malignancy. Midgut carcinoid tumor specimens were microdissected and expression levels of potential TAAs were investigated by quantitative real time PCR. HLA-A*0201-binding motifs were selected using HLA peptide binding prediction algorithms and stabilization of HLA-A*0201 was verified using TAP-deficient T2 cells. Peripheral blood of midgut carcinoid patients was analyzed for peptide epitope recognition and the feasibility of generating peptide-reactive CD8+ T cells in healthy blood donors was examined by an in vitro stimulation protocol using mature DCs. Activation of patient and healthy donor CD8+ T cells was analyzed by intracellular flow cytometry staining of interferon γ. Chromogranin A (CGA), tryptophan hydroxylase 1 (TPH-1), vesicular monoamine transporter 1 (VMAT-1), caudal type homeobox transcription factor 2 (CDX-2), and islet autoantigen 2 (IA-2) are properly expressed by midgut carcinoid tumor cells, with CGA mRNA expressed to greatest level. Midgut carcinoid patients have increased frequencies of peripheral blood CD8+ T cells recognizing a pool of HLA-A*0201 peptides derived from these proteins compared to healthy age-matched individuals. Activated peptide-specific CD8+ T cells could also be generated in healthy blood donors by in vitro stimulation. We have identified a number of immunogenic midgut carcinoid-associated peptide epitopes recognized by CD8+ T cells. We show that midgut carcinoid patients display immune recognition of their tumors. Memory CD8+ T cells in patient blood are of great interest when pursuing an immunotherapeutic treatment strategy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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Full text from SpringerLink