Poster Presentation 11th Annual Conference of the International Chemical Biology Society 2022

Identification of small molecule enhancers of natural killer-cell tumoricidal activity (#107)

Aylin Binici 1 2 , Elisabeth Hennes 1 2 , Alisa Reich 1 2 , Sandra Koska 1 2 , Christiane Pfaff 1 3 , Sonja Sievers 1 3 , Slava Ziegler 1 , Herbert Waldmann 1 2
  1. Max-Planck-Institute of Molecular Physiology, Dortmund, NORTH RHINE-WESTPHALIA, Germany
  2. Technical University Dortmund, Dortmund
  3. Compound Management and Screening Center (COMAS), Dortmund

Natural Killer (NK) cells are part of the innate immune system and exhibit many advantageous properties justifying their use for immunotherapeutic purposes. They have the unique ability to sense malignant changes in cells and eradicate them without prior sensitization. Therefore, NKs are critical for the mammalian first-line defense against tumor development. Within the tumor microenvironment (TME), cancer cells co-opt immune inhibitory pathways and reprogram surrounding cell types to promote tumor growth. This allows cancer cells to become less immunogenic, which supports the escape of immune cell mediated cytotoxicity. Many strategies are currently being developed to harness the anticancer potential of NKs and overcome resistance of cancer cells. However, previous clinical studies using NK cells to treat diverse malignancies had mixed outcomes due to lacking efficacy. For this reason, novel strategies to enhance and preserve NK cell tumoricidal activity within the TME are demanded. To harness the power of NKs, we developed a phenotypic co-culture-based system that mimics the TME to monitor NK cell-mediated cancer cell cytolysis. This assay proved to be suitable for the identification of novel small-molecule enhancers of NK-cell tumoricidal activity.

 

Literature

  1. Menon, S., Shin, S. & Dy, G. Advances in Cancer Immunotherapy in Solid Tumors. Cancers (Basel) 8, doi:10.3390/cancers8120106 (2016).
  2. Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331, 1565-1570, doi:10.1126/science.1203486 (2011).
  3. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. & Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3, 991-998, doi:10.1038/ni1102-991 (2002).
  4. Esfahani, K. et al. A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol 27, S87-S97, doi:10.3747/co.27.5223 (2020).