Identification and characterisation of the expression, regulation and function as well as the clinical relevance of HLA-G regulatory microRNAs in solid tumors

• Applicant: Professorin Dr. Barbara Seliger
• Subject Area: Hematology, Oncology ; Immunology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274305846

The non-classical HLA-G molecule is frequently overexpressed in human tumors of distinct origin. By interaction with different receptors of immune effector cells HLA-G-positive cells escape immune surveillance by T and NK cells. This aberrant expression of HLA-G is mediated by distinct molecular mechanisms, such as epigenetic, transcriptional and post-transcriptional control. Recently, some HLA-G specific microRNAs have been identified, which downregulate the expression of HLA-G thereby modulating the anti-viral and anti-tumoral immune response. The aim of this project is to (i) systematically identify the whole spectrum of human microRNAs, which modulate the constitutive and regulated HLA-G expression in tumors, (ii) to characterize the expression pattern, (iii) the regulation, and (iv) the function of these HLA-G specific microRNAs as well as to (v) determine their clinical relevance in tumors of distinct histology and its correlation with the immune cell infiltration. (vi) In addition, the HLA-G expression of tumors will be manipulated in vitro and in vivo using HLA-G regulating miRs/antagomiRs and tested for their anti-tumoral activity. This project will contribute to an increased knowledge of HLA-G regulatory microRNAs as novel strategy for the treatment of HLA-G expressing tumors.

• DFG Programme: Research Grants