ArticleCancer immunology, immunotherapy : CII2008
CD8+ T cells against multiple tumor-associated antigens in peripheral blood of midgut carcinoid patients.
Article in Cancer immunology, immunotherapy : CII, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 28 citations in OpenAlex.
- Serum Inflammation-based Scores in Endocrine Tumors.The Journal of clinical endocrinology and metabolism · 2021Review
- Article
- Novel immunotherapy strategies for treatment of neuroendocrine neoplasms.Translational gastroenterology and hepatology · 2020Review
- Analysis of the immune landscape of small bowel neuroendocrine tumors.Endocrine-related cancer · 2019Article
- Predictive value of preoperative peripheral blood neutrophil/lymphocyte ratio for lymph node metastasis in patients of resectable pancreatic neuroendocrine tumors: a nomogram-based study.World journal of surgical oncology · 2017Article
- Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2013Article
- Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth.Cancer research · 2008Article
- Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1.OncoimmunologyArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeThe 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
designMidgut 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.
resultsChromogranin 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.
conclusionWe 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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