Blocking regulatory T cell-attracting chemokines as therapeutic goal for the treatment of HCC

• Applicant: Professor Dr. David Anz
• Subject Area: Gastroenterology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223990502

Hepatocellular carcinomas (HCC) express several well-described tumor-specific antigens recognizable by cytotoxic T cells. Anti-tumor immune responses can however be inhibited by regulatory T cells, a subpopulation of lymphocytes specialized in suppressing innate and adaptive immunity. Tumor-infiltrating regulatory T cells have been shown to dampen tumor immunity in several types of human cancer. In HCC high numbers of infiltrating regulatory T cells have been correlated with poor prognosis. How these regulatory T cells are attracted to the tumors is so far unknown. By joining our and other research group PI’s experimental experience we will identify chemokines involved in regulatory T cell migration to HCC and will develop tools to target them therapeutically. Human HCC specimens will be examined for expression of regulatory T cell-attracting chemokines, in particular for CCL22, CCL17, CXCL12 and CCL28. In large series of tissue specimens the amounts of chemokines will be correlated to regulatory T cell infiltration and to disease outcome. To functionally investigate the role of candidate chemokines we will over-express CCL22 and CCL17 in murine HCC cell lines and analyze regulatory T cell recruitment and tumor growth in mice. Regulatory T cell attracting chemokines will be targeted therapeutically using blocking antibodies in a murine model of HCC. In summary, the aim of our project is to identify chemokines responsible for regulatory T cell recruitment to HCC in order to determine their role in tumor progression and as a therapeutic target.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Stefan Endres