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CD8(+) T cells agai...
CD8(+) T cells against multiple tumor-associated antigens in peripheral blood of midgut carcinoid patients
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- Vikman, Sofia (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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- Giandomenico, Valeria (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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- Sommaggio, Roberta (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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- Öberg, Kjell (författare)
- Uppsala universitet,Medicin
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- Essand, Magnus (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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- Tötterman, Thomas H. (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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(creator_code:org_t)
- 2007-08-24
- 2008
- Engelska.
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 57:3, s. 399-409
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 gamma. 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.
Nyckelord
- midgut carcinoid
- antigens
- HLA-A*0201
- CD8(+) T cells
- IFN gamma
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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