Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm

Wang, Jen C.; Kundra, Ajay; Andrei, Mirela; Baptiste, Stacey; Chen, Chi; Wong, Ching; Sindhu, Hemant

doi:10.1016/j.leukres.2016.02.004

Cited by 52 publications

(53 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results on DCs are in line with previous reports showing an increased level of myeloid derived suppressor cells in MPN 33 confirming that the increased release of immature myeloid cells led to the reduction of differentiated myeloid subsets as DCs. All together, these findings can explain, at least in part, the high infection rates seen in MF patients that are further exacerbated by ruxolitinib, 34 a JAK1/2 inhibitor affecting DCs differentiation and function in vitro.…”

Section: Discussionsupporting

confidence: 93%

Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis

et al. 2017

View full text Add to dashboard Cite

Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2,13 exon-9 CALR mutation and 5 triple negative). In comparison to healthy donors, patients presented a reduced amount of circulating dendritic cells (DCs) associated with a defective ability of monocytes in differentiating into DCs. In addition, we found a reduction in circulating T-helper (Th)1 and Th17 and hypo-functional innate lymphoid cells (ILC). Results analyzed according to the mutational status showed that patients carrying JAK2 mutation had a reduction in Th17, myeloid-DCs and effector Tregs as well as increased ILC1 and cytokine producing Tregs. The CALR mutated patients revealed high ILC3 levels, reduced Th1 and their monocytes had a reduced capacity to mature into fully committed DCs. Their Tregs were also less effective in inhibiting the proliferation of autologous effector T-cells due to an increased proliferative status induced by CALR mutation. Triple negative patients presented a reduced amount of total circulating CD3, effectors Tregs and Th1 with increased ILC1. Overall, we have demonstrated that in MF different mutations lead to phenotypic and functional alterations in different immune subsets that may have a potential role in disease progression and susceptibility to infections.

show abstract

Section: Discussionsupporting

confidence: 93%

Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…MDSCs form phenotypically heterogeneous groups of cells that share the capacity to exert a suppressor function (8,9). The level of these cells increases in the presence of infection (10,11) as well as in the presence of several types of murine (4,11,12) and human cancers (13)(14)(15). Conversely, Tregs comprise a subtype of Th-cells marked by the expression of high levels of the interleukin-2 receptor α chain (IL-2Rα-chain) (CD25) and forkhead box transcription factor P3 (Foxp3) (6,(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities

et al. 2017

View full text Add to dashboard Cite

To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4+ and CD8+ T cells as well as CD4+ Foxp3+ T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model. In addition, the subcutaneous model, but not the pulmonary model, displayed a Th1 polarization bias. This bias was characterized by decreased IL-4, IL-9, and IL-10 production, whereas the pulmonary model displayed increased production of IL-10. These results suggest that the mode of tumor development has differential effects on systemic immunity that may, in turn, influence approaches to treatment of cancer patients.

show abstract

“…5 In this regard, it is intriguing to speculate that an impaired immunosurveillance may contribute to the increased incidence of LPN, since MPN has been recognized as a model of inflammatory disease ("a human inflammation model of cancer development") 61 in which cytokines play a significant role in disease initiation and progression. 62 Several immune abnormalities have been, indeed, reported in MPN, regardless of any pharmacological intervention; among these, a significant increase in myeloid-derived suppressor cells, which may negatively interfere with immunosurveillance, has been reported, 63 while NK cells have been found to be functionally defective, with impaired degranulation and killing capacity. 64 Moreover, MPN patients have shown reduced levels of regulatory T cells, 65 which are also involved in tumor immunosurveillance, though data on this topic were not always concordant.…”

Section: Is There a Role For Cytoreductive Drugs For The Concomitanmentioning

confidence: 99%

Myeloproliferative and lymphoproliferative disorders: State of the art

Rumi

Baratè

Benevolo

et al. 2019

Hematological Oncology

View full text Add to dashboard Cite

Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal disorders complicated mainly by vascular events and transformation to myelofibrosis (for PV and ET) or leukemia. Although secondary malignancies, in particular, lymphoproliferative disorders (LPNs), are rare, they occur at a higher frequency than found in the general population, and there has been recent scientific discussion regarding a hypothetical relationship between treatment with JAK inhibitors in MPN and the risk of development of LPN. This has prompted increased interest regarding the coexistence of MPN and LPN. This review focuses on the role of JAK2 and the JAK/STAT pathway in MPN and LPN, whether there is a role for the genetic background in the occurrence of both MPN and LPN and whether there is a role for cytoreductive drugs in the occurrence of both MPN and LPN. Furthermore, whether an increased risk of lymphoma development is limited to patients who receive the JAK inhibitor ruxolitinib, is a more general phenomenon that occurs following JAK1/2 inhibition or is associated with preferential JAK1 or JAK2 targeting is discussed.

show abstract

Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm

Cited by 52 publications

References 43 publications

Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis

Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis

Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities

Myeloproliferative and lymphoproliferative disorders: State of the art

Contact Info

Product

Resources

About