In C04, M. Hölzel will seek to enhance chemokine expression by SCLC cells, in order to promote T cell recruitment and efficacy of immune checkpoint inhibition (ICI). The H3K9 histone dimethyltransferases EHMT1/2 were identified as drug targets to enforce interferon-stimulated gene and chemokine expression. M. Hölzel will thus analyze the molecular mechanisms of EHMT1/2 function and the implications of their inhibition. Furthermore, combinations of EHMT1/2 inhibitors with ICI will be explored in vivo expecting improved therapeutic efficacy through enhanced T cell recruitment. Clinical relevance of the findings will be assessed with the aim of identifying genomic and non-genomic correlates of EHTM1/2 inhibitor efficacy. By working with B04, C04 will search for additional other epigenetic modifiers that control interferon-stimulated gene and chemokine expression in SCLC.
University Hospital Bonn
Institute of Experimental Oncology