Overproduction of IL-7, IL-10 and TGF-β1 in Multiple Myeloma

Kröning, H.; Täger, Michael; Thiel, U; Ittenson, A; Reinhold, Dirk; Bühling, Frank; Kettner, E.; Ansorge, Siegfried

doi:10.1159/000203602

Cited by 23 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PDI is a redox-active enzyme that has four Trx motifs, and here we find that it is also up-regulated at the later stages of differentiation. This is in accordance with a parallel study that showed an increase of PDI expression in activated B cells [47,48] Membrane-bound protein disulfide isomerase (PDI) is involved in regulation of surface expression of thiols and drug sensitivity of B-CLL cells [48]. We recently obtained evidence that TNF-receptor clustering and signaling is redox-regulated by PDI (Hossain and Rosén, to be published).…”

Section: Discussionsupporting

confidence: 81%

Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell

et al. 2004

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 81%

Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell

et al. 2004

View full text Add to dashboard Cite

“…MM cells produce a number of immune modulators that may suppress the anticancer immune response, such as TGF-β, interleukin-10 (IL-10), vascular endothelial growth factor and mucin-1. 31 These factors could block DC differentiation and function, resulting in immature and/or partially differentiated DCs. 12 These dysfunctional DCs may process and present cancer antigens and stimulate Treg-cell differentiation and expansion instead of promoting an anti-MM immune response.…”

Section: Discussionmentioning

confidence: 99%

Overcoming Immune Tolerance Against Multiple Myeloma With Lentiviral Calnexin-engineered Dendritic Cells

et al. 2008

View full text Add to dashboard Cite

The key to successful cancer immunotherapy is to induce an effective anticancer immunity that will overcome the acquired cancer-specific immune tolerance. In this study, we found that dendritic cells (DCs) from multiple myeloma (MM) patients suppressed rather than induced a cancer cell-specific immune response. We demonstrated that CD4(+)CD25(high) T cells from MM patients suppressed the proliferation of activated peripheral blood lymphocytes. Further analysis illustrated that MM cell lysates or MM-specific idiotype immunoglobulins (MM Id-Ig) specifically induced the expansion of peripheral CD4(+)CD25(high)FoxP3(high) T regulatory (Treg) cells in vitro. Supraphysiological expression of calnexin (CNX) using lentiviral (LV) vectors in DCs of MM patients overcame the immune suppression and enhanced MM-specific CD4 and CD8 T-cell responses. However, overexpression of CNX did not affect the peripheral expansion of Treg cells stimulated by MM antigens. Thus, the immune suppression effect of Treg cells in cancer patients may be overcome by improving antigen processing in DCs, which in turn may lower the activation threshold of the immune effector cells. This concept of modulating anticancer immunity by genetically engineering cancer patients' DCs may improve immunotherapeutic regimens in cancer treatment.

show abstract

“…Cells within the MM niche, i.e. bone marrow stromal cells, produce large quantities of IL-6, IL-7, IL-8, and TGFβ which regulate the growth and survival of malignant cells, maintain the cytokine feedback loops, and sustain the pro-tumorigenic environment [23], [24], [25]. Autocrine production of IL-15 has been shown to contribute to MM cell survival [26].…”

Section: Introductionmentioning

confidence: 99%

The Systemic Cytokine Environment Is Permanently Altered in Multiple Myeloma

et al. 2013

View full text Add to dashboard Cite

Multiple myeloma (MM) is an incurable bone marrow malignancy of the B cell lineage. Utilizing multiplex Luminex technology we measured levels of 25 cytokines in the plasma of normal donors (n = 177), those with monoclonal gammopathy of undetermined significance (n = 8), and MM patients (n = 55) with either active disease, on treatment, or in remission. The cytokine levels were compared between normal donors and MM patients as well as between various phases of MM, and discriminant analysis was used to create a predictive classification model based on the differentially expressed cytokines. Evaluating age- and gender-dependence of cytokine expression, we determined that with age there is a shift toward a pro-inflammatory environment. Moreover, we observed a strong gender bias in cytokine expression. However, the profile of differentially expressed cytokines was heavily skewed toward an anti-inflammatory, pro-tumorigenic response in patients with MM. Significantly, our predictive model placed all patients in remission in the same category as those with active disease. Thus, our study demonstrates that the homeostasis of systemic cytokines is not restored when MM patients enter remission, suggesting that once an individual has cancer, the microenvironment is permanently altered and the system is primed for a relapse.

show abstract

Overproduction of IL-7, IL-10 and TGF-β1 in Multiple Myeloma

Cited by 23 publications

References 0 publications

Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell

Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell

Overcoming Immune Tolerance Against Multiple Myeloma With Lentiviral Calnexin-engineered Dendritic Cells

The Systemic Cytokine Environment Is Permanently Altered in Multiple Myeloma

Contact Info

Product

Resources

About