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Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic
Sung-Eun Lee1,2, Feng Wang3, Maison Grefe4
1Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
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. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape.
Conclusions:
Analysis of tumor-immune landscape in MDS during immunotherapy provides clinical response biomarkers.
