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Cancer Immunology, Immunotherapy

Erschienen in:

01.03.2008 | Original Article

CD8⁺ T cells against multiple tumor-associated antigens in peripheral blood of midgut carcinoid patients

verfasst von: Sofia Vikman, Valeria Giandomenico, Roberta Sommaggio, Kjell Öberg, Magnus Essand, Thomas H. Tötterman

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2008

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Abstract

Purpose

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.

Experimental design

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.

Results

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.

Conclusion

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.

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Titel: CD8+ T cells against multiple tumor-associated antigens in peripheral blood of midgut carcinoid patients
verfasst von: Sofia Vikman
Valeria Giandomenico
Roberta Sommaggio
Kjell Öberg
Magnus Essand
Thomas H. Tötterman
Publikationsdatum: 01.03.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 3/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0382-4

Springer Medizin

CD8⁺ T cells against multiple tumor-associated antigens in peripheral blood of midgut carcinoid patients