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Title:
Immune responses to p53 in patients with cancer:enrichment in tetramer+ p53 peptide-specific T cells and regulatory T cells at tumor sites | Cancer Immunology, Immunotherapy
Description:
Objective: A majority of human cancers, including head and neck cancer (HNC), “overexpress” p53. Although T cells specific for wild-type (wt) sequence p53 peptides are detectable in the peripheral blood of patients with HNC, it is unknown whether such T cells accumulate in tumor-involved tissues. Also, the localization of “regulatory” T cells (Treg) to tumor sites in HNC has not been investigated to date. Methods: Tumor infiltrating lymphocytes (TIL), tumor-involved or non-involved lymph node lymphocytes (LNL) and peripheral blood mononuclear cells (PBMC) were obtained from 24 HLA-A2.1+ patients with HNC. Using tetramers and four-color flow cytometry, the frequency of Treg and CD3+CD8+ T cells specific for wt p53 epitopes as well as their functional attributes were determined. Results: The CD3+CD8+ tetramer+ cell frequency was significantly higher (P<0.001) in TIL than autologous PBMC as was the percentage of CD4+CD25+ T cells (P<0.003). TIL were enriched in FOXp3+, GITR+ and CTLA-4+ Treg. CD8+ TIL had low Ζ expression and produced little IFN-γ after ex vivo stimulation relative to autologous PBMC or PBMC from NC. Conclusions: Anti-wt p53 epitope-specific T cells and Treg preferentially localize to tumor sites in patients with HNC. However, despite enrichment in tumor peptide-specific T cells, the effector cell population (CD3+CD8+) in TIL or PBMC was unresponsive to activation in the tumor microenvironment enriched in Treg.
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Keywords {🔍}
cells, cancer, google, scholar, article, pubmed, cas, whiteside, patients, regulatory, tumor, cdcd, immunol, human, head, neck, cell, peripheral, blood, res, deleo, specific, wildtype, treg, lymphocytes, til, access, tumors, pittsburgh, privacy, cookies, content, research, immunology, immune, hnc, pbmc, clin, donnenberg, publish, search, tetramer, sites, albers, kim, theresa, immunity, peptide, data, information,
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p53 wild-type epitope-specific cd8+cd28- t-cell subset tumor-suppressor gene-product p53 anti-wt p53 epitope-specific month download article/chapter nih grants po1-de12321 tumor-involved lymph nodes late-stage ovarian cancer wt p53 epitopes tetramer+ p53 peptide-specific article cancer immunology full article pdf anti-p53 cytotoxic human cd4+cd25+ cells privacy choices/manage cookies sequence p53 peptides neck cancer research epitope-loss variants tnf receptor superfamily stout family fund related subjects removing cd25+cd4+ tumor escape access tumor peptide-specific tumor-induced death peptide-mhc class human cd4+cd25+ tumor-involved tissues low ζ expression clinical laboratory immunology cd4+cd25+ regulatory regulatory cd4+cd25+ lymphoid suppressor cells european economic area wild-type vivo stimulation relative naturally occurring population ligand mediates resistance hillman cancer center t-cell recognition specific immune response tumor infiltrating lymphocytes tumor-infiltrating lymphocytes conditions privacy policy somatic point mutations oral oncol 32b effector cell population accepting optional cookies color flow cytometry predicts reduced survival
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- Ramsdell F (2003) Foxp3 and natural regulatory T cells: key to a cell lineage?
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headline:Immune responses to p53 in patients with cancer:enrichment in tetramer+ p53 peptide-specific T cells and regulatory T cells at tumor sites
description:Objective: A majority of human cancers, including head and neck cancer (HNC), “overexpress” p53. Although T cells specific for wild-type (wt) sequence p53 peptides are detectable in the peripheral blood of patients with HNC, it is unknown whether such T cells accumulate in tumor-involved tissues. Also, the localization of “regulatory” T cells (Treg) to tumor sites in HNC has not been investigated to date. Methods: Tumor infiltrating lymphocytes (TIL), tumor-involved or non-involved lymph node lymphocytes (LNL) and peripheral blood mononuclear cells (PBMC) were obtained from 24 HLA-A2.1+ patients with HNC. Using tetramers and four-color flow cytometry, the frequency of Treg and CD3+CD8+ T cells specific for wt p53 epitopes as well as their functional attributes were determined. Results: The CD3+CD8+ tetramer+ cell frequency was significantly higher (P<0.001) in TIL than autologous PBMC as was the percentage of CD4+CD25+ T cells (P<0.003). TIL were enriched in FOXp3+, GITR+ and CTLA-4+ Treg. CD8+ TIL had low Ζ expression and produced little IFN-γ after ex vivo stimulation relative to autologous PBMC or PBMC from NC. Conclusions: Anti-wt p53 epitope-specific T cells and Treg preferentially localize to tumor sites in patients with HNC. However, despite enrichment in tumor peptide-specific T cells, the effector cell population (CD3+CD8+) in TIL or PBMC was unresponsive to activation in the tumor microenvironment enriched in Treg.
datePublished:2005-06-16T00:00:00Z
dateModified:2005-06-16T00:00:00Z
pageStart:1072
pageEnd:1081
sameAs:https://doi.org/10.1007/s00262-005-0670-9
keywords:
TIL
Tetramers
wt p53 epitopes
CD4+CD25+ T cells
Regulatory T cells (Treg)
Tumor escape
Oncology
Immunology
Cancer Research
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headline:Immune responses to p53 in patients with cancer:enrichment in tetramer+ p53 peptide-specific T cells and regulatory T cells at tumor sites
description:Objective: A majority of human cancers, including head and neck cancer (HNC), “overexpress” p53. Although T cells specific for wild-type (wt) sequence p53 peptides are detectable in the peripheral blood of patients with HNC, it is unknown whether such T cells accumulate in tumor-involved tissues. Also, the localization of “regulatory” T cells (Treg) to tumor sites in HNC has not been investigated to date. Methods: Tumor infiltrating lymphocytes (TIL), tumor-involved or non-involved lymph node lymphocytes (LNL) and peripheral blood mononuclear cells (PBMC) were obtained from 24 HLA-A2.1+ patients with HNC. Using tetramers and four-color flow cytometry, the frequency of Treg and CD3+CD8+ T cells specific for wt p53 epitopes as well as their functional attributes were determined. Results: The CD3+CD8+ tetramer+ cell frequency was significantly higher (P<0.001) in TIL than autologous PBMC as was the percentage of CD4+CD25+ T cells (P<0.003). TIL were enriched in FOXp3+, GITR+ and CTLA-4+ Treg. CD8+ TIL had low Ζ expression and produced little IFN-γ after ex vivo stimulation relative to autologous PBMC or PBMC from NC. Conclusions: Anti-wt p53 epitope-specific T cells and Treg preferentially localize to tumor sites in patients with HNC. However, despite enrichment in tumor peptide-specific T cells, the effector cell population (CD3+CD8+) in TIL or PBMC was unresponsive to activation in the tumor microenvironment enriched in Treg.
datePublished:2005-06-16T00:00:00Z
dateModified:2005-06-16T00:00:00Z
pageStart:1072
pageEnd:1081
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keywords:
TIL
Tetramers
wt p53 epitopes
CD4+CD25+ T cells
Regulatory T cells (Treg)
Tumor escape
Oncology
Immunology
Cancer Research
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