한빛사논문
- 조회427
Sung-Eun Lee 1,2, Feng Wang 3, Maison Grefe 4, Abel Trujillo-Ocampo 4, Wilfredo Ruiz-Vasquez 4, Koichi Takahashi 3,5, Hussein A Abbas 5, Pamella Borges 5,6, Dinler Amaral Antunes 6, Gheath Al-Atrash 1,4,5, Naval Daver 5, Jeffrey J Molldrem 1,4,5, Andrew Futreal 3, Guillermo Garcia-Manero 4, Jin S Im 1,4,5
1Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
2Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
3Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
4Department of Hematopoietic Biology and Malignancy, Division of Cancer Medicine, The University of Texas M.D, Anderson Cancer Center, Houston, Texas.
5Department of Leukemia, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
6Department of Biology and Biochemistry, The University of Houston, Houston, Texas.
*Corresponding Author: Jin S. Im
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.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-06-07)
- 국내+국외 연구진
- 의약학 > 응용의학
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