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Interrogate Tumor-Immune Interactions in AML Patients Receiving Immune Checkpoint Inhibitors

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  • 9:00 am (PDT)

Abstract

Introducing Nanostring’s latest spatial platform, CosMx Spatial Molecular Imager (SMI).  Offering high-plex, multi-omic in situ analysis coupled with single-cell to subcellular resolution in intact Formalin-Fixed Paraffin-Embedded (FFPE) and fresh frozen tissue sample, learn how CosMx SMI advances spatially resolved single-cell applications including cell atlassing, ligand-receptor interactions, and neighborhood analysis.

In today’s talk, Dr. Chen Zhao will elaborate on how his lab spatially resolved the tumor-immune interactions in the bone marrow microenvironment to gain a deeper understanding of the tumor-immune microenvironment in R-AML during combination ICI treatment. Relapsed or refractory Acute Myeloid Leukemia (R-AML) is a deadly disease with an inadequate response rate to current treatments. Recent advances in immunotherapy shed light on R-AML, and several clinical trials have shown promising potential for combining immune checkpoint inhibitors (ICIs) with hypomethylating agents. Comprehending the tumor-immune microenvironment in R-AML during combination ICI treatment is urgently needed for developing better therapeutics and stratifying treatment strategies. To dissect the tumor-immune interactions in the bone marrow microenvironment, Dr. Zhao’s team employed NanoString GeoMx Digital Spatial Profiler (DSP), CosMx SMI, and performed a spatial-transcriptomic analysis of patients with R-AML who received pembrolizumab and decitabine. Comparing the transcriptomic profiles and TCR clonalities of tumor-interacting T cells, bystander T cells, and other cells at baseline, post-pembrolizumab treatment, and post-decitabine, led to the identification of R-AML’s suppressive immune microenvironment and immune cells’ responses to ICI and hypomethylating agent. The spatial-transcriptomic profiles of T cells, stromal cells, and leukemia cells in patients with R-AML were obtained at different treatment points. The TCR-specific probes were able to track T cell clonal changes during treatments. R-AML harbored a complex tumor immune microenvironment and diverse T cell clonality.

Learning Objectives

  • Understand how Nanostring’s GeoMx DSP and CosMx SMI spatial platforms were used to determine the spatial transcriptomic profiles of T cells, stromal cells, and leukemia cells in patients with R-AML
  •  Learn how CosMx SMI is able to spatially track T-cell clonal changes during treatment
  • Learn how diverse T-cell clonality impacts the tumor-immune microenvironment in R-AML during combination ICI treatment

Dr. Chen Zhao, MD

Thoracic Oncologist, Immunologist, Physician-scientist. Center for Cancer Research, National Cancer Institute

Speaker’s Bio

Dr. Chen Zhao is a medical oncologist, immunologist, and physician-scientist focusing on tumor immunology and immunotherapy. He specializes in developing novel immunotherapeutics and using advanced tissue imaging techniques and spatial-transcriptomic analysis to understand the three-way interactions among tumor cells, the immune system, and the microbiota in the tumor microenvironment over the course of cancer initiation, progression, and therapeutic response.