Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL

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Hohtari , H , Bruck , O , Blom , S , Turkki , R , Sinisalo , M , Kovanen , P E , Kallioniemi , O , Pellinen , T , Porkka , K & Mustjoki , S 2019 , ' Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL ' , Leukemia , vol. 33 , no. 7 , pp. 1570-1582 . https://doi.org/10.1038/s41375-018-0360-1

Title: Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL
Author: Hohtari, Helena; Bruck, Oscar; Blom, Sami; Turkki, Riku; Sinisalo, Marjatta; Kovanen, Panu E.; Kallioniemi, Olli; Pellinen, Teijo; Porkka, Kimmo; Mustjoki, Satu
Contributor organization: HUS Comprehensive Cancer Center
Hematologian yksikkö
Institute for Molecular Medicine Finland
HUSLAB
Medicum
Department of Pathology
Department of Clinical Chemistry and Hematology
Precision Systems Medicine
Date: 2019-07
Language: eng
Number of pages: 13
Belongs to series: Leukemia
ISSN: 0887-6924
DOI: https://doi.org/10.1038/s41375-018-0360-1
URI: http://hdl.handle.net/10138/303963
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.
Subject: ACUTE LYMPHOBLASTIC-LEUKEMIA
T-CELLS
IMATINIB MESYLATE
TUMOR
CHEMOTHERAPY
THERAPY
IMMUNOPHENOTYPE
IMMUNOSCORE
MECHANISMS
CONTEXTURE
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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