Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

Giuliani, Nicola; Airoldi, Irma

doi:10.1158/1078-0432.ccr-11-1724

Cited by 11 publications

(8 citation statements)

References 74 publications

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“…On the other hand, we found an inverse correlation between BM levels of IL-27 and PD-L1 expression on monocytes and %CD8 + PD-1 + cells, independently from the stage of disease. These results are in line with IL-27 anti-tumoral activity in MM ( 24 ); despite the recent findings on its role in PD-L1 in vitro up-regulation in different solid cancer cells ( 39 ).…”

Section: Discussionsupporting

confidence: 78%

“…We also checked BM levels of the main MM pro-survival cytokine, IL-6, which is known to be higher in MM patients as compared with HDs ( 23 ); our data confirmed the increased BM IL-6 levels in patients with advanced stage of disease (SMM vs. MMD vs. MMR pg/ml: 2.830 vs. 8.270 vs. 7.625, Kruskal-Wallis test, p = 0.03) ( Figure 4B ); however, we did not find any correlation with PD-L1/PD-1 expression on PCs (Spearman r: 0.042, p = 0.77) and BM microenvironment cells (data not shown). We then measured BM levels of IL-27, with demonstrated anti-tumor activity in MM ( 24 ), in 33 patients, including 10 SMM, 13 MMD, and 10 MMR. In line with its role in MM, we found that IL-27 levels progressively decrease in the advanced stages of disease, even without reaching a statistical significance (SMM vs. MMD vs. MMR pg/ml: 1303 vs. 870.1 vs. 478.7, Kruskal-Wallis test, p = 0.07) ( Figure 4C ).…”

Section: Resultsmentioning

confidence: 99%

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PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

et al. 2021

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BackgroundThe PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies.MethodsThe PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients.ResultsFirst, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16− cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between %CD14+PD-L1+ and %CD8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells.ConclusionsOur data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment.

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

et al. 2021

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“…Therefore, a large number of miRNAs were expected to be found differentially expressed in AS T cells. In addition, miR-4449 is overexpressed in multiple myeloma [ 26 ], and it is interesting that the abnormal expression of IL-23 plays a role in the pathogenesis of multiple myeloma [ 27 ]. The role of other miRNAs deserves further study.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of interleukin-23-regulated miRNAs in T cells from patients with ankylosing spondylitis

Lai

Tung

et al. 2018

Arthritis Res Ther

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BackgroundInterleukin (IL)-23 can facilitate the differentiation of IL-17-producing helper T cells (Th17). The IL-23/IL-17 axis is known to play a key role in the immunopathogenesis of ankylosing spondylitis (AS). We hypothesized that the expression of microRNAs (miRNAs, miRs) would be regulated by IL-23 and that these miRNAs could participate in the immunopathogenesis of AS.MethodsExpression profiles of human miRNAs in K562 cells, cultured in the presence or absence of IL-23 for 3 days, were analyzed by microarray. Potentially aberrantly expressed miRNAs were validated using T-cell samples from 24 patients with AS and 16 control subjects. Next-generation sequencing (NGS) was conducted to search for gene expression and biological functions regulated by specific miRNAs in the IL-23-mediated signaling pathway.ResultsInitial analysis revealed that the expression levels of 12 miRNAs were significantly higher, whereas those of 4 miRNAs were significantly lower, in K562 cells after coculture with IL-23 for 3 days. Among these IL-23-regulated miRNAs, the expression levels of miR-29b-1-5p, miR-4449, miR-211-3p, miR-1914-3p, and miR-7114-5p were found to be higher in AS T cells. The transfection of miR-29b-1-5p mimic suppressed IL-23-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation in K562 cells. After NGS analysis and validation, we found that miR-29b-1-5p upregulated the expression of angiogenin, which was also upregulated in K562 cells after coculture with IL-23. Increased expression of miR-29b-1-5p or miR-211-3p could enhance interferon-γ expression.ConclusionsAmong the miRNAs regulated by IL-23, expression levels of five miRNAs were increased in T cells from patients with AS. The transfection of miR-29b-1-5p mimic could inhibit the IL-23-mediated STAT3 phosphorylation and might play a role in negative feedback control in the immunopathogenesis of AS.

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“…Only early B lymphocytes, germinal center B cells, and plasma cells have a functional IL-23R [191,192]. In tumor cells, the IL-23R molecule is present on myeloma cells, follicular lymphoma, acute lymphoblastic leukemia cells, and diffuse large B cell lymphoma cells [193,194].…”

Section: Effects Of Cytokines On the Onset Progression And Complicamentioning

confidence: 99%

Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role

Allegra

Musolino

Tonacci

et al. 2020

Cancers

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B-cell chronic lymphocytic leukemia (B-CLL) is the main cause of mortality among hematologic diseases in Western nations. B-CLL is correlated with an intense alteration of the immune system. The altered functions of innate immune elements and adaptive immune factors are interconnected in B-CLL and are decisive for its onset, evolution, and therapeutic response. Modifications in the cytokine balance could support the growth of the leukemic clone via a modulation of cellular proliferation and apoptosis, as some cytokines have been reported to be able to affect the life of B-CLL cells in vivo. In this review, we will examine the role played by cytokines in the cellular dynamics of B-CLL patients, interpret the contradictions sometimes present in the literature regarding their action, and evaluate the possibility of manipulating their production in order to intervene in the natural history of the disease.

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Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

Cited by 11 publications

References 74 publications

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

Aberrant expression of interleukin-23-regulated miRNAs in T cells from patients with ankylosing spondylitis

Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role

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