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Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 4674
© 2005 American Society of Clinical Oncology
Tumor infiltrating dendritic cells (DC) in prostate cancer (PCa): Implications for vaccine therapy
G. S. Chatta,
M. Aalamian,
E. Huland,
H. Huland,
I. Tourkova,
G. Shurin and
M. Shurin
Univ of Pittsburgh, Pittsburgh, PA; Univ of Hamburg, Hamburg, Germany
4674
Background: The ability of DC to migrate to sites of tumor, capture antigens, migrate to regional lymph nodes, and activate naïve T cells, is key to the induction of in vivo anti-tumor immunity. In fact a correlation between the number of DC infiltrating tumor and a generally more favorable clinical course, has been reported for a number of cancers, including PCa. However, there is little information on the viability and propensity for apoptosis of DC infiltrating tumors in vivo. Here we report on a immunohistochemical analyses of DC from PCa of different pathological stages. Methods: The analyses were conducted in accordance with IRB procedures, on fresh PCa tissue from 18 radical prostatectomy specimens performed at the Dept of Urology, Hamburg, Germany. Patient (pt) characteristics: median age 59 yr; pT2, n=5; pT3, n=10; pT4, n=3. Pts were analyzed as groups of localized (pT2) or advanced (pT3, pT4) PCa along with matched normal prostate tissue. DC distribution in prostatic tissue was assessed with immunohistochemical stains for the following markers: CD83 for mature DC; S100 for tissue DC; and CD1a for immature DC. To evaluate DC apoptosis, double stains were done for S100/TUNNEL in all specimens, and CD83/TUNNEL and CD1a/TUNNEL in some cases. Additional stains for T lymphocytes (CD4 and CD8) and macrophages (CD68) were also performed. The intensity of staining was graded from 0 to 4, and the expression level of markers between groups was compared using non-parametric statistics. Results: The expression of DC markers in pT2 vs pT3–4 tumors was as follows: CD 83, 1.5±0.24 vs 1.0±0.21(p 0.05); S100, 3.5±0.5 vs 0.75±0.37(p<0.01); CD1a, 0.15±0.01 vs 0.93±0.31(p<0.05); CD68, 1.25±0.25 vs 1.92±0.19(p<0.05). Thus mature DC preferentially infiltrate localized tumors and more advanced tumors have an immature DC infiltrate and an excess of macrophages. Two-color staining with S100/TUNNEL demonstrated a DC apoptotic index of 6±2.9 in pT3-T4 PCa vs 1.3±0.9 in pT2 PCa ((p<0.05). Conclusions: Tumor grade determines both DC phenotype, as well as DC apoptosis within tumor tissue (PCa) in vivo. Furthermore, preliminary analysis also reveals an inverse relationship between PSA expression and CD83 expression in tumor samples.
No significant financial relationships to disclose.
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