Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

Lullo, Giulia Di; Marcatti, Magda; Protti, Maria Pia

doi:10.1080/2162402x.2015.1093278

Cited by 13 publications

(19 citation statements)

References 30 publications

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“…Additionally, the frequency of Th17 cells and the ratio between Th17 cells and plasma cells in the BM were the highest in Early-MM Vk*MYC mice, which nicely correlated with increased levels of IL-17 in the BM of SMM patients that more rapidly progressed to MM. Together with the recent evidence that Th17 cells are also enriched in the BM of some MGUS-SMM patients 56 , our data support a much earlier role for IL-17 in this neoplasm.…”

Section: Discussionsupporting

confidence: 89%

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

et al. 2018

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The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.

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Section: Discussionsupporting

confidence: 89%

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

et al. 2018

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“…11,[26][27][28] Numerous studies have shown that the level of Th17 cells in PBMCs are significantly elevated in ND MM patients compared with healthy donors. 24,29 Our study also yielded the same results. On this basis, we tracked Th17 cell levels at different treatment stages of the disease and found that the level of Th17 cells were increased in PR patients and decreased to almost normal levels compared with that of ND patients when CR was achieved, but increased again when the disease relapsed.…”

Section: Discussionsupporting

confidence: 82%

“…The percentage of Th17 cells in PBMCs of the Con group was 0.8009 (AE0.10359%) and the fluctuation range was 0.5% to 1.5%, which was consistent with the literature reports.l 24,25 Although the percentage of Th17 cells in PBMCs of ND MM patients was significantly higher than that of healthy persons, its fluctuation range was much wider than that of healthy persons. Some patients had lower Th17 levels than healthy persons, some patients had the same level as healthy persons, and some patients had higher Th17 levels than healthy persons.…”

Section: Three Levels Of Th17 Cells In Pbmcs Of Nd MM Patientssupporting

confidence: 89%

A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma

Zhang

Zhou

et al. 2020

Clinical Lymphoma Myeloma and Leukemia

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T helper 17 (Th17) cells changed with different treatment stages of multiple myeloma (MM). The level of Th17 cells in the newly diagnosed group was higher than that in the controls. MM patients with normal Th17 cell levels had the shortest time to complete remission, the highest complete remission rate and the longest progression-free survival. Th17 cell level in newly diagnosed MM patients can be used as a prognostic indicator. Background: T helper 17 (Th17) cells are a subset of CD4-positive T cells, which secrete interleukin 17 and specifically express the retinoic acid receptor-related orphan receptors gt gene. Recently, Studies have shown that the level of Th17 cells in peripheral blood of newly diagnosed multiple myeloma (MM) patients is significantly higher than that of healthy persons. Th17 cells play an important role in the immune microenvironment of MM and interact with tumor cells, osteoclasts, and osteoblasts. Th17 cells might be a potential therapeutic target for MM patients. Patients and Methods: In this study, we further tracked the levels of Th17 cells in peripheral blood of 56 patients with MM from newly diagnosed to partial remission to complete remission to relapse and 11 healthy donors. Results: The level of Th17 cells increased further when the disease reached partial remission, decreased to normal level when it reached complete remission, and increased again when the disease recurred. In addition, we also found that in newly diagnosed MM patients, Th17 cell levels fluctuated greatly; not all patients were upregulated, and patients with normal Th17 cell levels had the highest chance of complete remission. Conclusion: Th17 cells contribute to the stratification of different treatment stages of MM patients. The level of Th17 cells in patients with newly diagnosed MM is associated with the treatment outcome of complete remission.

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“…IRF8 induces activation-induced cytidine deaminase, which is a key enzyme catalyzing somatic hypermutations of plasma cells 21 . Similar to IRF4, IRF8 transcriptional activity in multiple myeloma may also be related to differentiation of T helper (T H ) 17 cells, which have a regulatory effect on bone morphogenesis-related onset of multiple myeloma 22 . IRF8 has been reported to act as an intrinsic transcriptional inhibitor of T H 17 cells, at least partly through its physical interaction with retinoic acid receptor-related orphan receptor RORγt 23 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma

et al. 2019

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Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, T H 17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response.

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Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

Cited by 13 publications

References 30 publications

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma

Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma

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