Immunologic Predictors for Clinical Responses During Immune Checkpoint Blockade in Patients With Myelodysplastic Syndromes

Authors

Sung-Eun Lee
Feng Wang
Maison Grefe
Abel Trujillo-Ocampo
Wilfredo Ruiz-Vasquez
Koichi Takahashi
Hussein A Abbas
Pamella Borges
Dinler Amaral Antunes
Gheath Al-Atrash
Naval Daver
Jeffrey J Molldrem
Andrew Futreal
Guillermo Garcia-Manero
Jin S Im

Publication Date

5-15-2023

Journal

Clinical Cancer Research

Abstract

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.

Keywords

Humans, Immune Checkpoint Inhibitors, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Immunotherapy

Comments

Supplementary Material

PMID: 36988276

DOI

10.1158/1078-0432.CCR-22-2601

PMID

36988276

PMCID

PMC10192218

PubMedCentral® Posted Date

November 2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes