Poster Presentation 37th Lorne Cancer Conference 2025

Tackling immune escape: identifying novel targets and pathways involved in the regulation of CD155 (#137)

Fenna F Feenstra 1 2 , Marius Jentzsch 3 , Caroline Fandrey 3 , Maike Effern 3 , Emily Lelliott 2 , Dillon Corvino 1 , Michael Hölzel 3 , Jonathan Schmid-Burgk 1 , Marco J Herold 2 4 5 6 , Tobias Bald 1
  1. Institute of Experimental Oncology, University Hospital Bonn, Bonn, NRW, Germany
  2. Olivia Newton-John Cancer Research Institute, ONJCRI, Heidelberg, Victoria, Australia
  3. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, NRW, Germany
  4. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  5. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  6. School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia

Despite the great success, a considerable group of patients are resistant to current approved cancer immunotherapies. CD155, an adhesion molecule of the Nectin-like family and ligand for immunomodulatory receptors including the immune checkpoint receptor TIGIT and the activating receptor CD226, is known to be overexpressed in many different tumor types. Our lab has recently shown that CD155-expressing tumor cells downregulate the activating receptor CD226 on tumor infiltrating CD8+ T cells, which renders tumor-infiltrating T cells dysfunctional and contributed to resistance to cancer immunotherapies. In contrast, little is known about the cell intrinsic mechanisms regulating the expression of CD155. We have identified several human melanoma cell lines that express high levels of CD155 and generated inducible or dead Cas9-expressing variants. We conducted a genome-wide CRISPR-screen to identify novel pathways and potentially druggable molecules involved in the regulation of CD155. Currently we are in the process of validation. Validated hits might enable us to reduce or completely abolish CD155 expression in cancer cells in order to improve the efficacy of cancer immunotherapies.