TY - JOUR
T1 - Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes
AU - Lee, Sung Eun
AU - Wang, Feng
AU - Grefe, Maison
AU - Trujillo-Ocampo, Abel
AU - Ruiz-Vasquez, Wilfredo
AU - Takahashi, Koichi
AU - Abbas, Hussein A.
AU - Borges, Pamella
AU - Antunes, Dinler Amaral
AU - Al-Atrash, Gheath
AU - Daver, Naval
AU - Molldrem, Jeffrey J.
AU - Futreal, Andrew
AU - Garcia-Manero, Guillermo
AU - Im, Jin S.
N1 - Publisher Copyright:
©2023 American Association for Cancer Research.
PY - 2023/5/15
Y1 - 2023/5/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-22-2601
DO - 10.1158/1078-0432.CCR-22-2601
M3 - Article
C2 - 36988276
AN - SCOPUS:85159734686
SN - 1078-0432
VL - 29
SP - 1938
EP - 1951
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -