CD14+HLA-DRlow/− expression: A novel prognostic factor in chronic lymphocytic leukemia

Liu, Jinlin; Zhou, Yongchao; Huang, Qiang; Qiu, Liannv

doi:10.3892/ol.2014.2808

Cited by 33 publications

(32 citation statements)

References 15 publications

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“…In turn, this would be associated with inferior patient outcomes. In fact, one report identified an association between elevated MDSC levels and inferior prognosis in CLL [23]. …”

Section: Discussionmentioning

confidence: 99%

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

et al. 2016

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Background Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. Methods We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Results Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk-stratification of CLL patients for TTT. Conclusions Elevated AMC at diagnosis is associated with inferior CLL patient outcomes and accelerated disease progression. Monocyte-derived cells in the CLL microenvironment promote CLL cell survival and proliferation. Together, these findings suggest that monocytes and monocyte-derived cells are rational therapeutic targets in CLL.

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“…In turn, this would be associated with inferior patient outcomes. In fact, one report identified an association between elevated MDSC levels and inferior prognosis in CLL [23]. …”

Section: Discussionmentioning

confidence: 99%

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

et al. 2016

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“…In addition to macrophages dysfunction, myeloid DCs from CLL patients are also severely defective, unable to effectively drive a Th1 response and display downregulation of MHC-II and upregulation of PD-L1 (Orsini et al 2003, 2004; Hanna et al 2015). Another emerging population of suppressive cells, the so-called myeloid-derived suppressor cells (MDSC), which are characterized as CD14 + cells lacking HLA-DR expression (HLA-DR lo ), have been found at increased absolute numbers in CLL patients, with higher levels of MDSCs correlated with disease progression and poorer prognosis (Jitschin et al 2014; Liu et al 2015). MDSCs suppressed in vitro T cell activation and proliferation and induced suppressive regulatory CD4 + T cells (T reg ) in CLL (Jitschin et al 2014).…”

Section: Cll As a Model System To Study Interactions Between Tumor Anmentioning

confidence: 99%

Coevolution of Leukemia and Host Immune Cells in Chronic Lymphocytic Leukemia

Purroy

2017

Cold Spring Harb Perspect Med

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Cumulative studies on the dissection of changes in driver genetic lesions in cancer across the course of disease have provided powerful insights into the adaptive mechanisms of tumor in response to the selective pressures of therapy and environmental changes. In particular, the advent of next-generation sequencing (NGS)-based technologies and its implementation for the large-scale comprehensive analyses of cancers have greatly advanced our understanding of cancer as a complex dynamic system wherein genetically distinct subclones interact and compete during tumor evolution. Aside from genetic evolution arising from interactions intrinsic to the cell subpopulations within tumors, it is increasingly appreciated that reciprocal interactions between the tumor cell and cellular constituents of the microenvironment further exert selective pressures on specific clones that can impact the balance between tumor immunity and immunologic evasion and escape. Herein, we review the evidence supporting these concepts, with a particular focus on chronic lymphocytic leukemia (CLL), a disease that has been highly amenable to genomic interrogation and studies of clonal heterogeneity and evolution. A better knowledge of the basis for immune escape has important clinical impact on prognostic stratification and on the pursuit of new therapeutic opportunities.

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“…These findings are in correspondence to previous reports dealing with murine models and additionally indicate an essential role of M‐MDSCs for human B‐cell immunity. Since malignant B‐cell transformations frequently go ahead with an increased number of circulating M‐MDSCs in patients, their expansion has been suggested a prognostic factor of B‐cell disease . Our results demonstrate a direct suppressive effect of CD14 + HLA‐DR − MDSCs on human B cells, thereby identifying these cells as potential future therapeutic target for the treatment of B‐cell malignancies.…”

Section: Discussionmentioning

confidence: 55%

Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro

et al. 2019

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Myeloid‐derived suppressor cells (MDSCs) are key regulators of immunity that initially have been defined by their ability to potently suppress T‐cell responses. Recent studies collectively demonstrate that the suppressive activity of MDSCs is not limited to T cells, but rather affects a broad range of immune cell subsets. However, relatively few studies have assessed the impact of MDSCs on B cells, particularly in the human context. Here, we report that human monocytic MDSCs (M‐MDSCs) significantly interfere with human B‐cell proliferation and function in vitro. We further show that the inhibition occurs independent of direct cell‐contact and involves the expression of suppressive mediators such as indoleamine 2, 3‐dioxygenase (IDO), arginase‐1 (Arg1), and nitric oxide (NO). In addition, our studies demonstrate that the suppression of B cells by M‐MDSCs is paralleled by a skewing in B‐cell phenotype and gene expression signatures. M‐MDSCs induced the downregulation of key surface markers on activated B cells, including IgM, HLA‐DR, CD80, CD86, TACI, and CD95. Concurrently, M‐MDSCs but not conventional monocytes elicited alterations in the transcription of genes involved in apoptosis induction, class‐switch regulation, and B‐cell differentiation and function. In summary, this study expands our understanding of the regulatory role of M‐MDSCs for human B‐cell responses.

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CD14+HLA-DRlow/− expression: A novel prognostic factor in chronic lymphocytic leukemia

Cited by 33 publications

References 15 publications

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

Coevolution of Leukemia and Host Immune Cells in Chronic Lymphocytic Leukemia

Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro

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