Epigenetic Regulation of Chermokine Expression in Prostate Cancer

摘要

Specific active immunotherapy is based on the principle that malignant cells contain immunogenic sites against which an antitumor immune response can be induced. Dendritic cells (DC) that acquire antigens from tumor cells are able to induce and regulate specific antitumor immunity. However, it is still unclear why the circulating DC do not induce efficient antitumor immunity in cancer patients. While successful immunotherapy requires a functional immune system, a defect in the immune response may contribute to tumor growth. Our major hypothesis was that loss of expression of chemokine CXCL14 by prostate cancer (PCa) cells plays an important role in PCa escape from immune recognition. To gain new insights into the functional interaction between DC and neoplastic cells, we proposed to analyze the effects of PCa on the chemotaxis of human DC in vitro and in vivo. Our Specific Aims were: 1. Characterize chemotactic activity of CXCL14 towards human DC in vitro. 2. Examine whether restoration of CXCL14 expression in PCa increases chemoattraction of DC both in vitro and in vivo. 3. Characterize epigenetic mechanisms of regulation of CXCL14 expression in PCa. The results of our studies allow us to conclude that epigenetic regulation of chemokine expression in PCa is a principal new mechanisms of tumor escape.