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Tytuł pozycji:

Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response

Tytuł :
Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response
Autorzy :
Ercolini, Anne M
Ladle, Brian H
Manning, Elizabeth A
Pfannenstiel, Lukas W
Armstrong, Todd D
Machiels, Jean-Pascal
Bieler, Joan G
Emens, Leisha A
Reilly, R Todd
Jaffee, Elizabeth M
Pokaż więcej
Temat :
Receptors, Interleukin-2 - immunology
Genes, erbB-2 - immunology
Cyclophosphamide - administration & dosage
Lymphocyte Activation - immunology
Epitopes, T-Lymphocyte - genetics, immunology
Immunotherapy, Adoptive
Mice
Article
Mice, Transgenic
Cancer Vaccines - administration & dosage, genetics
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes - immunology
Animals
Immunosuppressive Agents - administration & dosage
CD4-Positive T-Lymphocytes - immunology
Cell Communication - drug effects, immunology
Female
Antigens, Neoplasm - immunology
Mammary Neoplasms, Experimental - immunology, therapy
Vaccination
Cytotoxicity, Immunologic
Źródło :
The Journal of Experimental Medicine
The Journal of Experimental Medicine, Vol. 201, no. 10, p. 1591-602 (2005)
Wydawca :
The Rockefeller University Press, 2005.
Rok publikacji :
2005
Kolekcja :
Depot_Institutionel_de_lUniversite_catholique_de_Louvain_et_de_lUniversite_Saint-Louis
Depot_Institutionel_de_lUniversite_catholique_de_Louvain_et_de_lUniversite_Saint-Louis_enriched
Oryginalny identyfikator :
pmc: PMC2212915
pmid: 15883172
Język :
English
ISSN :
1540-9538
0022-1007
DOI :
10.1084/jem.20042167
A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8(+) T cell responses to a dominant peptide (RNEU(420-429)) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N-derived CD4(+)CD25(+) T cells. RNEU(420-429)-specific CD8(+) T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU(420-429)-specific CD8(+) T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4(+)CD25(+) T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8(+) T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.

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