Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes.

Purpose: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).

Experimental Design: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.

Results: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment.

Fidelity of peripheral blood for monitoring genomics and tumor immune-microenvironment in myelodysplastic syndromes.

The aim of this study is to investigate whether the peripheral blood (PB) can serve as a surrogate immune-microenvironment to bone marrow for genetic and immune monitoring in myelodysplastic syndrome (MDS). We compared the composition of T cell subsets and somatic mutation burden in 36 pairs of PB and matching bone marrow aspirate (BMA) using multi-parameter flow cytometry and NGS-based targeted sequencing analysis, respectively. Our immune-subset and NGS-based mutation analysis of BMA showed significant concordance with those of PB in MDS.

A Novel T-Cell Engaging Bi-specific Antibody Targeting the Leukemia Antigen PR1/HLA-A2.

Despite substantial advances in the treatment of acute myeloid leukemia (AML), only 30% of patients survive more than 5 years. Therefore, new therapeutics are much needed. Here, we present a novel therapeutic strategy targeting PR1, an HLA-A2 restricted myeloid leukemia antigen.