Dr. Chen Zhao, MD: Interrogating Tumor-Immune Interactions in AML Patients Receiving Immune Checkpoint Inhibitors

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

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.

For Research Use Only.  Not for Use in Diagnostic Procedures.