Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML

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http://hdl.handle.net/10138/237329

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Bruck , O , Blom , S , Dufva , O , Turkki , R , Chheda , H , Ribeiro , A , Kovanen , P , Aittokallio , T , Koskenvesa , P , Kallioniemi , O , Porkka , K , Pellinen , T & Mustjoki , S 2018 , ' Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML ' , Leukemia , vol. 32 , no. 7 , pp. 1643-1656 . https://doi.org/10.1038/s41375-018-0175-0

Title: Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML
Author: Bruck, Oscar; Blom, Sami; Dufva, Olli; Turkki, Riku; Chheda, Himanshu; Ribeiro, Antonio; Kovanen, Panu; Aittokallio, Tero; Koskenvesa, Perttu; Kallioniemi, Olli; Porkka, Kimmo; Pellinen, Teijo; Mustjoki, Satu
Other contributor: University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, HUSLAB
University of Helsinki, Doctoral Programme in Integrative Life Science
University of Helsinki, Department of Medicine
University of Helsinki, Doctoral Programme in Integrative Life Science
University of Helsinki, Doctoral Programme in Drug Research
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Clinical Chemistry and Hematology

















Date: 2018-07
Language: eng
Number of pages: 14
Belongs to series: Leukemia
ISSN: 0887-6924
DOI: https://doi.org/10.1038/s41375-018-0175-0
URI: http://hdl.handle.net/10138/237329
Abstract: Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia bone marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients' CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+ TIM3-CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.
Subject: CHRONIC MYELOID-LEUKEMIA
CHRONIC MYELOGENOUS LEUKEMIA
TREATMENT-FREE REMISSION
MOLECULAR RESPONSE
T-CELLS
CHRONIC-PHASE
STEM-CELLS
DEATH 1
IMATINIB
DISCONTINUATION
3122 Cancers
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