WT1-specific CD8 + cytotoxic T cells with the capacity for antigen-specific expansion accumulate in the bone marrow in MDS.
Bone marrow
CD8-positive T-lymphocytes
Immunoassay
Myelodysplastic syndrome
Wilms’ tumor 1
Journal
International journal of hematology
ISSN: 1865-3774
Titre abrégé: Int J Hematol
Pays: Japan
ID NLM: 9111627
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
29
11
2020
accepted:
13
01
2021
revised:
12
01
2021
pubmed:
28
1
2021
medline:
8
6
2021
entrez:
27
1
2021
Statut:
ppublish
Résumé
Wilms' tumor 1 (WT1) is a tumor-associated antigen and immunotherapy target in myelodysplastic syndrome (MDS). Further information is needed on the characteristics of WT1-specific CD8 + T cells to develop immunotherapeutic strategies for MDS. To clarify the frequency, distribution, and phenotype of WT1-specific CD8 + T cells, which occur innately in MDS patients, we analyzed paired peripheral blood (PB) and bone marrow (BM) samples from 39 patients with MDS or acute myeloid leukemia with myelodysplasia-related changes. The median frequency of WT1 tetramer-binding CD8 + T cells in the CD8 + T cell population was 0.11% in PB and 0.18% in BM. A further tetramer assay combined with mixed lymphocyte peptide culture (MLPC assay) was used to detect functional WT1-specific CD8 + T cells that could respond to the WT1 peptide. Functional WT1-specific CD8 + T cells were detected in BM in 61% of patients, which was significantly higher than in PB (23%, p = 0.001). The frequency of these cells estimated by the MLPC assay was tenfold higher in BM than in PB. The majority of WT1 tetramer-binding CD8 + T cells in BM had a unique phenotype with co-expression of CD39 and CXCR4. These findings will facilitate the development of novel immunotherapeutic strategies for MDS.
Identifiants
pubmed: 33502734
doi: 10.1007/s12185-021-03083-0
pii: 10.1007/s12185-021-03083-0
doi:
Substances chimiques
CD8 Antigens
0
WT1 Proteins
0
WT1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
723-734Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP17K09006
Organisme : Japan Society for the Promotion of Science
ID : JP18K07410
Organisme : Japan Society for the Promotion of Science
ID : JP16K09868
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