Characterization of γδ regulatory T cells from peripheral blood in patients with multiple myeloma

Ma, Ying; Lei, Huyi; Tan, Jie; Li, Xuan; Wu, Xiuli; Liu, Qifa

doi:10.1016/j.bbrc.2016.10.098

Cited by 12 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other groups have confirmed the emergence of regulatory/suppressor Vγ9Vδ2 T cells as a consequence of pAg activation in the presence of selected cytokines ( 69 , 70 ). Ma et al have reported an increased proportion of regulatory Vγ9Vδ2 T cells in the PB of MM patients which could suppress antimyeloma immune responses with the same efficiency of conventional Tregs ( 71 ).…”

Section: Strategies To Rescue Antitumor Vγ9vδ2 T-cell Function In Thementioning

confidence: 99%

Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression

et al. 2018

View full text Add to dashboard Cite

Vγ9Vδ2 T cells are non-conventional T cells with a natural inclination to recognize and kill cancer cells. Malignant B cells, including myeloma cells, are privileged targets of Vγ9Vδ2 T cells in vitro. However, this inclination is often lost in vivo due to multiple mechanisms mediated by tumor cells and local microenvironment. Multiple myeloma (MM) is a paradigm disease in which antitumor immunity is selectively impaired at the tumor site. By interrogating the immune reactivity of bone marrow (BM) Vγ9Vδ2 T cells to phosphoantigens, we have revealed a very early and long-lasting impairment of Vγ9Vδ2 T-cell immune functions which is already detectable in monoclonal gammopathy of undetermined significance (MGUS) and not fully reverted even in clinical remission after autologous stem cell transplantation. Multiple cell subsets [MM cells, myeloid-derived suppressor cells, regulatory T cells, and BM-derived stromal cells (BMSC)] are involved in Vγ9Vδ2 T-cell inhibition via several immune suppressive mechanisms including the redundant expression of multiple immune checkpoints (ICPs). This review will address some aspects related to the dynamics of ICP expression in the BM of MM patients in relationship to the disease status (MGUS, diagnosis, remission, and relapse) and how this multifaceted ICP expression impairs Vγ9Vδ2 T-cell function. We will also provide some suggestions how to rescue Vγ9Vδ2 T cells from the immune suppression operated by ICP and to recover their antimyeloma immune effector functions at the tumor site.

show abstract

Section: Strategies To Rescue Antitumor Vγ9vδ2 T-cell Function In Thementioning

confidence: 99%

Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression

et al. 2018

View full text Add to dashboard Cite

show abstract

“…On the other hand, regulatory γδT cells (γδTreg) are the recently reported subset of γδT cells characterized by both expressions of TCRγδ and Foxp3, with potential immunosuppressive functions ( 11 ). Studies have shown the potential role of γδ regulatory T cells in inhibiting antitumor immune responses in patients diagnosed with multiple myeloma ( 12 ). However, studies on the relation of γδT17 cells and γδTreg cells in ovalbumin (OVA)-induced asthma are poorly reported.…”

Section: Introductionmentioning

confidence: 99%

Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin

Xia

Zhang

Deng

et al. 2018

Braz J Med Biol Res

View full text Add to dashboard Cite

We aimed to explore the imbalance between the T helper 17 γδT cells (γδT17) and the regulatory γδT cells (γδTreg) in asthmatic mice. Male Balb/c mice were randomly divided into the normal control group and the asthmatic model group. The asthmatic model group mice were intraperitoneally injected with the mixture of ovalbumin (OVA)/Al(OH)3 and then activated by exposure of the animals to OVA atomization. Airway hyperresponsiveness (AHR) was determined by a non-invasive lung function machine. Hematoxylin and eosin and Alcian blue-periodic acid Schiff staining were done for histopathological analysis. Interleukin (IL)-17 and IL-35 levels in bronchoalveolar lavage fluid were detected by ELISA. The percentage of IL-17+ γδT cells and Foxp3+ γδT cells in spleen cells suspension were detected and the transcription levels of RORγt and Foxp3 in the lung tissue were determined. Compared with the normal control, the severity of airway inflammation and AHR were higher in the asthmatic mice. Furthermore, mice in the asthmatic group displayed significant increases of IL-17+ γδT cells, expression of IL-17A, and RORγt, whereas control mice displayed marked decreases of Foxp3+ γδT cells, expression of IL-35, and transcription factor Foxp3. In addition, the mRNA expression of RORγt was positively correlated with the percentage of IL-17+γδT cells, and the mRNA level of Foxp3 was positively correlated with the percentage of Foxp3+ γδT cells. The imbalance of γδT17/γδTreg in the asthmatic mice may contribute to the pathogenesis of OVA-induced asthma.

show abstract

“…We reported different hypothetical mechanism of anti-MM activity of zoledronic acid, for which there is actually no consensus, for this reason, according with the results found in solid tumors, we explored the contribution of bisphosphonates in anti-MM activity studying its potential anti-angiogenic effect based on modification of cytokines which are pivotal in this pathogenic mechanism [11][12][13][14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Annibali¹,

Petrucci²,

Tirindelli³

et al. 2017

J Blood Lymph

View full text Add to dashboard Cite

Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon's test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion. Conclusions:From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

show abstract

Characterization of γδ regulatory T cells from peripheral blood in patients with multiple myeloma

Cited by 12 publications

References 25 publications

Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression

Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression

Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Contact Info

Product

Resources

About