Certain cellular pathways were upregulated in patients with myelodysplastic syndromes (MDS) who responded to immunotherapy, according to a recent study.
Sung-Eun Lee, MD, PhD, of the University of Texas MD Anderson Cancer Center and the Catholic University of Korea and colleagues conducted the research.
The researchers aimed to determine immune-related biomarkers that would predict effective antitumor immunity in MDS during immunotherapy with or without a hypomethylating agent (HMA).
Dr. Lee and colleagues collected peripheral blood samples from 55 patients with MDS. They used the samples to perform immune-related gene expression profiling before and after the first treatment. They also assessed immune subsets and the T-cell receptor (TCR) repertoire in samples. Dr. Lee and colleagues additionally used the samples to identify mutations in 295 acute myeloid leukemia/MDS-related genes.
They found that patients who responded clinically and were treated with immunotherapy plus or minus an HMA—but not one alone—had a “significant” expansion of central memory CD8-positive T-cells.
Those patients also had “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 post-treatment,” according to Dr. Lee and colleagues.
The researchers found that autophagy, transforming growth factor beta (TGFβ), and T helper type 1 (Th1) differentiation pathways were the “most downregulated” in patients who did not respond after treatment. However, autophagy, TGFβ, and Th1 differentiation pathways were upregulated in patients who responded to therapy.
“Finally, [cytotoxic T-lymphocyte associated protein 4] but not [programmed cell death protein 1] blockade attributed to favorable changes in immune landscape,” Dr. Lee and colleagues wrote, concluding that analyzing the “tumor-immune landscape in MDS during immunotherapy provides clinical response biomarkers.”
Lee SE, Wang F, Grefe M, et al. Immunologic predictors for clinical responses during immune checkpoint blockade in patients with myelodysplastic syndromes. Clin Cancer Res. 2023:OF1-OF14. doi:10.1158/1078-0432.CCR-22-2601