Dirk Bausch

Focus of Research: Pancreatic cancer

Currently Attending:
Massachusetts General Hospital

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Colon carcinoma tumor immunology in the CT-26 mouse model: "immune escape" mechanisms

Co-Authors Baier P, Hopt UT

Tumor vaccination, which primarily activates cellular immunity, is a promising approach in the therapy of cancer. Experimental and clinical studies have proven its efficacy. However, several tumor immune escape mechanisms limit its success. The understanding of their action and their inhibition is a key step in the improvement of tumor vaccination response rates.
To characterize these immune escape mechanisms better, in this study, balb/c-mice were vaccinated with radiated CT-26-colon carcinoma cells twice 14 and 7 days before intraperitoneal injection of living tumor cells. 100% of the control (n=25), but only 14,7% of the vaccinated (n=34) group developed peritoneal carcinosis. To determine the cell lines involved in the vaccination response, CD4+-, CD8+- und NK1-cells were depleted via intraperitoneal antibody injection. 83% of the control, 50 % of the CD8+-, 100% of the NK1-depleted and 33% CD4+- depleted animals (n=6) developed peritoneal carcinosis. These results demonstrate a significant vaccination effect. Its basis is the activation of innate cellular immunity, especially of NK1+-cells.
2D gel electrophoresis yielded 1958 proteins. The comparison of protein expression among the groups showed 25 proteins with significant difference (p<0,001) in their expression pattern (0,01 %). Amongst several glucose metabolism enzymes, which were upregulated in the vaccinated group, Hdgfrp2 (hepatoma-derived growth factor related protein 2) was overexpressed, whereas Hspa4l (heat shock protein 4 like protein) was reduced in the vaccinated group. The proteomic basis of this effect is the reduced expression of Hspa4l, whose expression is immunogenic. Hdgfrp2 overexpression is a marker of cell dedifferentiation. To improve vaccination results, the addition of Hspa4l to the vaccine will be tested next.

presented at Chirurgisches Forum 2007

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