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Cited by 51Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyCancer Immunotherapy and Biomarkers

High immunogenic potential of p53 mRNA-transfected dendritic cells in patients with primary breast cancer

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Met, Özcan, Balslev, Eva, Flyger, Henrik, Svane, Inge Marie·2011·Breast Cancer Research and Treatment
DOI 10.1007/s10549-010-0844-9
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Abstract

As pre-existent immunity might be a reflection of an emerging anticancer response, the demonstration of spontaneous T-cell responses against tumor associated antigens (TAAs) in cancer patients may be beneficial before clinical development of dendritic cell (DC)-based cancer vaccines, because it will help to identify likely responders to TAAs among patients who qualify and may benefit from this form of immune therapy. This study aimed to determine pre-existent T-cell reactivity against the tumor suppressor protein p53 in breast cancer patients (BCP) at the time point of primary diagnosis. After a short-term stimulation with autologous wt p53 mRNA-transfected DCs, IFN-γ enzyme-linked immunosorbent spot (ELISPOT) analysis revealed p53-reactive T cells in the peripheral blood of more than 40% (15 of 36) of the tested patients. Both CD4(+) and CD8(+) p53-specific T cells secreted IFN-γ after stimulation with p53-transfected DCs. Interestingly, more than 72% (13 of 18) of patients with high p53 (p53(high)) expression in tumors were able to mount a p53-specific IFN-γ T-cell response, in contrast to only 10% (1 of 10) of healthy donors and 11% (2 of 18) of patients with low or absent p53 (p53(low)) expression in tumors. Furthermore, significantly higher secretion of IL-2 was detected in peripheral blood mononuclear cells after stimulation with p53-transfected DCs from patients with p53(high) tumor expression compared to patients with p53(low) tumor expression, whereas secretion of IL-10 was predominant in the latter group. The high frequency of spontaneous wt p53-reactive T cells detected in the peripheral blood of primary BCP with accumulation of p53 in tumor provides a rationale to consider DCs transfected with mRNA encoding wt p53 for clinical investigation in these patients.

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Authors
Met, Ö., Balslev, E., Flyger, H., & Svane, I. M.
Affiliations
Herlev Hospital (DK)
Corresponding author
Met, Özcan
ORCID
Venue
Breast Cancer Research and Treatment
Publisher
Springer Science and Business Media LLC
Published
2010-03-25
Volume
125
Issue
2
Pages
395-406
ISSN
  • 0167-6806 (ISSN-L)
  • 1573-7217
DOI
10.1007/s10549-010-0844-9
OpenAlex
W2033625614
Cited by
51
References
51
Citations by year
2026: 3 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 8 · 2014: 4 · 2013: 4 · 2012: 2
FWCI
1.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Breast Cancer Research and Treatment (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
p53, breast cancer, dendritic cells, mRNA transfection, tumor-associated antigens, pre-existing immunity, tumor suppressor proteins, dendritic cell-based cancer vaccine, interferon-gamma, interleukin-2, IL-10, CD4+ T cells, CD8+ T cells
MeSH terms
Breast Neoplasms, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Interferon-gamma, Interleukin-2, RNA, Messenger, T-Lymphocytes, Transfection, CD4-Positive T-Lymphocytes, Genes, p53, Tumor Suppressor Protein p53, Interleukin-10, CD8-Positive T-Lymphocytes

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