Characterization and clinical relevance of the alternative splicing from HLA-G and its regulators in the human renal cell carcinoma

• Applicant: Dr. Simon Jasinski-Bergner
• Subject Area: Nephrology ; Hematology, Oncology ; Immunology ; Pathology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 496182670

Under physiological conditions, the non-classical HLA class Ib molecule HLA-G is only expressed in immune privileged tissues mediating immunological tolerance by acting as ligand for the inhibitory receptors ILT2, ILT4, and KIR2DL4 upon various immune effector cells. The primary HLA-G transcript exerts alternative splicing, whereby 7 protein encoded splice variants exist, from which 4 are membrane bound (HLA-G1 to -G4) and 3 are soluble (HLA-G5 to -G7). A pathophysiological HLA-G expression can be frequently detected in different tumor diseases contributing to tumor immune evasion. In previous studies the working group and the applicant himself characterized the expression and the molecular regulation of HLA-G. Further analyses demonstrated a different splicing pattern of HLA-G transcript and protein in various tumor entities. Based on this data it is the aim of this grant to investigate the frequence of the single HLA-G isoforms, to identify HLA-G relevant splice factors and regulators, and to investigate their expression in regard to their influence on tumor biological as well as tumor immunological functions in the renal cell carcinoma (RCC). Furthermore, the composition of the soluble and membrane bound HLA-G isoforms and the identified HLA-G relevant splicing factors/regulators will be analyzed in clinical RCC tissue specimen as well as in patient serum samples also in regard to the patient's response to immune therapies within a pilot study.

• DFG Programme: Research Grants