2007 Fiscal Year Final Research Report Summary
Development of novel diagnostic techniques and therapeutic approaches using anti-p53 immune response
| Project/Area Number |
17591775
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | University of Yamanashi (2007)
Gunma University (2005-2006) |
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Principal Investigator |
CHIKAMATSU Kazuaki University of Yamanashi, Faculty of Medicine, Dept. of Otolaryngology-Head and Neck Surgery, Assistant Prof (30301378)
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| Co-Investigator(Kenkyū-buntansha) |
FURUYA Nobuhiko Gunma University, Graduate School of Medicine, Dept of Otolaryngology-Head and Neck Surgery, Professor (80107606)
MIYASHITA Motoaki Gunma University, Graduate School of Medicine, Dept. of Otolaryngology-Head and Neck Surgery, Assistant Prof (30400740)
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| Project Period (FY) |
2005 – 2007
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| Keywords | p53 / CTL / helper T cell / antibody / regulatory T cells |
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| Research Abstract |
The p53 gene has been shown to be frequently mutated, and alteration in p53 can result in the accumulation of p53 molecules in tumors, which is recognized by the immune system. Evidence has accumulated indicating that the pattern of anti-p53 T cell responses in cancer patients might be regulated by various factors. In this study, we investigated associations of the patients' immune status, anti-p53 T cell responses, p53 accumulation, and clinicopathological factors for development of novel diagnostic techniques and therapeutic approaches.
1. The percentage of myeloid, but not plasmacytoid DCs, was significantly lower and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy donors, and the proportion of total circulating DCs was inversely correlated with that of regulatory CD4(+)CD25(+) T cells (Treg).
2. Treg was increased in the patients, and the percent of Treg inversely correlated with that of total CD8+ T cells, Tcl cells, and Tc2 cells.
3. CD8+ T cells in 7/10 normal donors and 11/23 subjects with SCCHN responded to at least one of the wt p53 peptides. CD8+ T cell precursors responsive to wt p53 epitopes were detected in the circulation of most subjects with early disease, and an elevated blood Tc1/Tc2 ratio distinguished wt p53 peptide responders from non-responders.
4. Eleven (57.9%) of 19 patients tested had a detectable Th1 and/or Th2 responses to wt p53 peptides. Moreover, 2 (12.5%) of 8 post-operative patients had Th responses to wt p53 peptides. Four (80.0%) of 5 patients with early disease showed anti-p53 Th2 response. In contrast, 5 (83.3%) of 6 patients with advanced disease showed anti-p53 Th2 responses.
5. FOXP3 mRNA expression in patients of tumor burden was significantly higher compared to that in patients with no evidence of disease.
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