American Association for Cancer Research
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Figure S2 from Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes

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posted on 2023-05-15, 08:20 authored by 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

Figure S2. Schema for study design

Funding

catholic medical center research foundation

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (Khalifa Institute)

Emerson Collective (Emerson)

University of Texas MD Anderson Cancer Center (MD Anderson)

Welch Foundation (The Welch Foundation)

Lydia Hill Foundation

Anna Darko Foundation

National Cancer Institute cancer center support

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ARTICLE ABSTRACT

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). 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. 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. Analysis of tumor–immune landscape in MDS during immunotherapy provides clinical response biomarkers.

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