Webinar on Immuno-Oncology by Rima AIT-BELKACEM, PhD

Ranging from monoclonal antibodies to complex cellular vaccines, cancer immunotherapy englobes treatments that harness and enhance the innate powers of the patient’s immune system to fight cancer. Recently, by integrating available and new knowledges on the unique aspects of immune therapeutic approaches, the immuno-oncology framework provides a set of methodological improvements for the development of cancer immunotherapies.

In this context, IDO inhibitors move center stage in immunotherapy. Indoleamine 2,3-dioxygenase 1 (IDO-1) is an intracellular immune checkpoint protein that catalyzes the breakdown of the essential amino acid tryptophan (Trp). Dysregulation of this enzyme can result in the suppression of an appropriate immune response by macrophages and T-cells to cancer. Inhibition of IDO-1 has been shown to reinvigorate the natural immune response to cancer cells. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by LC-MS/MS analysis in human plasma, cerebrospinal fluid and brain. At this point, a lack of histological localization prevents from microenvironment tumor metabolic interactions understanding. Whereas, the development of immunotherapies such as IDO1 inhibitors requires a deep understanding of the immune system and cancer cells interplay and biomarkers characterization.

In this presentation, we will present the latest development to monitor the distribution and absolute quantification of Trp and its principal metabolite (Kynurenine, Kyn) by High-resolution MALDI imaging (Solarix 7T, Bruker Daltonics) in transfected murine tumor models expressing various levels of IDO1. High definition overlays between the IDO1 enzyme and its Kyn product, as well as an analytical confirmation using LC-MS/MS analysis were performed. Finally, this proof-of-concept study has also highlighted more metabolic signatures as myeloid and glycolysis markers translating many immune consequences:

  • Inhibition of T cell effector function and metabolism, Activation of regulatory T cell function/differentiation
  • Generation of tolerogenic Dendritic Cells
  • Promotion of M2-Macrophages…

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