Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL.
Leukemia
; 33(7): 1570-1582, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-30635636
ABSTRACT
As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Trasplante de Células Madre Hematopoyéticas
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Linfocitos T CD8-positivos
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Microambiente Tumoral
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Células Supresoras de Origen Mieloide
/
Macrófagos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Finlandia