Different recovery patterns of CMV-specific and WT1-specific T cells in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: Impact of CMV infection and leukemia relapse

Frontiers in Immunology

Immunology

Per Ljungman¹  Xiao-Hua Luo²  Qingda Meng³  Thomas Poiret³  Zhenjiang Liu³  Anurupa Nagchowdhury³ 

[1]Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Division of Hematology, Stockholm, Sweden

[2]Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

[3]Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

[4]Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

[5]Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

关键词: cytomegalovirus;    WT1 = Wilms tumor 1;    immune reconstitution;    stem cell transplantation;    acute myeloid leukemia (AML);   

DOI  :  10.3389/fimmu.2022.1027593

 received in 2022-08-25, accepted in 2022-11-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

In allogeneic hematopoietic cell transplantation (allo-HSCT), both virus-specific T cells and leukemia-specific T cells need to be reconstituted to protect patients from virus infections and primary disease relapse. Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allo-HSCT. Emerging data indicate that CMV reactivation is associated with reduced risk of leukemia relapse in patients with acute myeloid leukemia (AML) undergoing allo-HSCT. In a cohort of 24 WT1+ AML patients during the first year following HSCT, CMV specific CD8+ T cells (CMV-CTL) reconstituted much faster than WT1-specific CD8+ T cell (WT1-CTL) after allo-SCT. Moreover, CMV-CTL expressed lower levels of exhaustion markers and were more functional as identified by production of IFN-γ/TNF-α and expression of Eomes/T-bet. Interestingly, our patients with CMV reactivation presented higher frequency of CMV-CTL, lower levels of Eomes+T-bet- and higher levels of Eomes+T-bet+ expression in response to WT1 and CMV pp65 antigen during the first year after transplantation as compared to patients without CMV reactivation. Kinetics of CMV-CTL and WT1-CTL after transplantation might be associated with measurable residual disease and later leukemia relapse. Our results support that CMV reactivation, aside from the CMV-CTL reconstitution, could influence WT1-CTL reconstitution after allo-HSCT, thus potentially contributing to the remission/relapse of AML.

【 授权许可】

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Copyright © 2023 Luo, Poiret, Liu, Meng, Nagchowdhury and Ljungman