In this 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 NanoStringGeoMx 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’sGeoMx 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