Aktivierende anti-CD4O-Antikörper führen zu intratumoraler T-Lymphozytenmigration und Wachstumshemmung beim experimentellen Leberkarzinom
Introduction: As could be shown previously anti-CD4O antibodies activate CD4O molecules and improve the antigen presentation of malignant tumor cells. The aim of our study was to investigate the effect of anti-CD4O antibodies in liver cancer. Methods: The model of hepatocellular cancer (MH 3924) in the rat liver was used. The animals received anti-CD4O antibodies or 0.9% NaCl solution i. p. On day 6 tumor volume was measured and intravital microscopy (IVM) was performed quantifying leukocyte adherence and blood flow in the postcapillary venules. After IVM the hepatoma was removed and immunohistological analysis of CD4- and CD8-T-lymphocyte migration was performed. Results: The tumor volume was significantly decreased in the treated animals compared with the untreated animals (p<0.01). The mean blood flow in the tumor venules was not changed significantly (p > 0.5). The high-affinity and low-affinity leukocyte-endothelium interaction in the tumor and in the tumor surrounding area was significantly increased in the treated animals (p < 0.01). The number of cytotoxic CD8-T cells and CD4-T cells in the tumor and in the tumor surrounding area were significantly increased (p < 0.01) in the treated animals compared with the untreated animals. Conclusion: Therapy with anti-CD4O antibodies results in an increase of leukocyte-endothelium interaction, migration of CD4-/CD8-T cells into the tumor and inhibition of tumor growth. We postulate that these effects of anti-CD4O antibodies therapy could be utilized in the immunotherapy of liver cancer.
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