Bone marrow dendritic cell aggregates associate with systemic immune dysregulation in chronic myelomonocytic leukemia
Year: 2020
Type: article
Abstract: Systemic immune tolerance is not well-characterized in chronic myelomonocytic leukemia (CMML). Due to the presence of clonal plasmacytoid dendritic cells (pDC) in CMML, and the established association of lymph node indoleamine 2,3-dioxygenase-1 (IDO1)-positive (+) DC populations (IDC) with systemic immune tolerance in other malignant contexts, we sought to determine the association of IDO1 expression and bone marrow (BM) DC populations with systemic T-cell compartment changes using primary CMML patient samples (BM, plasma, and peripheral blood mononuclear cells) via immunohistochemistry (IHC), liquid chromatography-mass spectrometry (LC-MS), and time-of-flight mass cytometry (CyTOF). Our results highlight that aggregate BM IDC (CD123 and/or CD11c positive) occur in 33% CMML patients at any disease time-point (IHC), correlate with accentuated tryptophan catabolism (LC-MS, increased kynurenine level, median 4.7 versus 3 microM, P=0.049*), systemic regulatory T-cell expansion (CyTOF, %parent cell type, 14.5 versus 4.9%, P=0.04*) and play a role in disease progression, as evidenced by a higher rate of transformation to acute myeloid leukemia (41 versus 13%, P=0.002**), when compared to CMML patients without BM IDC. Our data also highlight a perturbed immune system in CMML with specific systemic immune signatures, particularly type 1, IL-17 producing helper T, CD4 terminal effector and natural killer cell suppression. Key Points Aggregate IDO1+ dendritic cell populations occur in the CMML bone marrow microenvironment, and their presence correlates with disease progression. Systemic immune microenvironment signatures in CMML indicate an altered T- and natural killer (NK)-cell balance. Specifically, suppression of type 1 helper T (Th1), IL-17 producing helper T (Th17), CD4 terminal effector and NK cells. IDO1+ bone marrow dendritic cell populations in CMML are associated with a T-cell compartment shift towards a regulatory T cell phenotype.
Source: Blood Advances
Authors: Abhishek A. Mangaonkar, Kaaren K. Reichard, Moritz Binder, Giacomo Coltro, Terra L. Lasho, Ryan M. Carr, April Chiu, Vivian Negron, Mehrdad Hefazi, Theodora Anagnostou, Michael M. Timm, James W. Hiebert, Jose C. Villasboas, Wilson I. Gonsalves, Naseema Gangat, Mithun Shah, Hassan B. Alkhateeb, Aref Al-Kali, Michelle A. Elliott, Kebede H. Begna, Alexandra P. Wolanskyj-Spinner, Mark R. Litzow, William J. Hogan, Stephen M. Ansell, Animesh Pardanani, Ayalew Tefferi, Mrinal M. Patnaik
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W3095055145