Deciphering the Complexity of the Acute Leukemia Immunological Microenvironment with 3D Biology™ Technology
|SPEAKER:||Doug Hinerfeld, Ph.D., Principal Product Application Scientist, NanoString Technologies; Sergio Rutella, M.D., Ph.D., Professor of Cancer Immunotherapy, John van Geest Cancer Research Centre, Nottingham Trent University|
Dec 05, 2017
Therapeutic strategies in patients with acute myeloid leukemia (AML) have remained relatively unchanged over the last 30 years. The development and delivery of new therapeutic strategies for high-risk AML, including immunotherapy, therefore remains a priority.
Tumor phenotypes are dictated not only by the neoplastic cell component, but also by the tumor microenvironment, which includes immune and inflammatory cells and mediators. Leukemia cells avoid host immune surveillance to promote tumor survival and progression. A key pathway mediating feedback inhibition and hindering anti-tumor immunity involves indoleamine 2,3-dioxygenase-1 (IDO1), an interferon (IFN)-g-inducible molecule.
NanoString’s 3D Biology™ Technology, which enables simultaneous profiling of any combination of SNV, RNA, protein, and phospho-protein targets with as few as 5,000 cells or just two successive 5 micron FFPE slices, was used in this research study to collect comprehensive molecular profiles across the biological heterogeneity of childhood and adult AML, with the aim to identify new molecular targets for specific immunologic subtypes of AML.
Bone marrow (BM) specimens from 70 patients with non-promyelocytic AML were profiled on the nCounter® system. Ninety BM samples were analyzed with the nCounter PanCancer Immune Profiling Panel. The Vantage 3D DNA:RNA:Protein Heme alpha assay was used to dissect the intracellular signaling pathways that are activated in leukemia cell lines in response to IFN-g. The assay profiles 180 mRNA species involved in heme-oncology pathways, >38 total and phosphorylated proteins, and >124 single nucleotide variants relevant to hematological malignancies. BM biopsies from patients with AML were also analyzed with NanoString’s Digital Spatial Profiling Technology to investigate co-localization of CD8+ T cells and “actionable” negative immune checkpoints, such as PD-L1, and to characterize the quality of the BM-infiltrating T cells.
In conclusion, this research study has identified heterogeneous immunological profiles in children and adults with AML at different disease stages. From a clinical standpoint, ‘immune enriched’ AML might be amenable to immunotherapy approaches tailored to the BM microenvironment, including blockade of co-inhibitory molecules and/or small-molecule IDO1 inhibitors.
Join us to learn more about how the combined analysis of SNV, mRNA, and protein expression on the nCounter system enabled a comprehensive characterization of the molecular landscape of leukemia cells.