The Immune Microenvironment of Myeloma

Noonan, Kimberly; Borrello, Ivan

doi:10.1007/s12307-011-0086-3

Cited by 45 publications

(51 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[7][8][9][10] Accordingly, B-cell precursors and normal plasma cells are compromised, and immune paresis is also a consistent finding in newly-diagnosed MM patients. 11 In turn, effector cells such…”

Section: Introductionmentioning

confidence: 79%

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

et al. 2012

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 79%

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

et al. 2012

View full text Add to dashboard Cite

“…Interactions with BM-MSCs enhanced MM cell growth, survival and drug-resistance. 1,6,7 TNFa and TGFb have been reported to upregulate VCAM-1 and ICAM-1 expression and trigger IL-6 secretion in BMMSCs. 47 We add here an important novel contribution of IL-13 in these functions.…”

Section: Patients Were Cd4mentioning

confidence: 99%

Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival

et al. 2015

View full text Add to dashboard Cite

There is increased production of plasmacytoid dendritic cells (pDCs) in the bone marrow (BM) of multiple myeloma (MM) patients and these favor Th22 cell differentiation. Here, we found that the frequency of interleukin (IL)-22 C IL-17 ¡ IL-13 C T cells is significantly increased in peripheral blood (PB) and BM of stage III and relapsed/refractory MM patients compared with healthy donors and patients with asymptomatic or stage I/II disease. Th22 cells cloned from the BM of MM patients were CCR6 C CXCR4 C CCR4 C CCR10 ¡ and produced IL-22 and IL-13 but not IL-17. Furthermore, polyfunctional Th22-Th2 and Th22-Th1 clones were identified based on the co-expression of additional chemokine receptors and cytokines (CRTh2 or CXCR3 and IL-5 or interferon gamma [IFNg], respectively). A fraction of MM cell lines and primary tumors aberrantly expressed the IL-22RA1 and IL-22 induced STAT-3 phosphorylation, cell growth, and resistance to drug-induced cell death in MM cells. IL-13 treatment of normal BM mesenchymal stromal cells (MSCs) induced STAT-6 phosphorylation, adhesion molecule upregulation, and increased IL-6 production and significantly favored MM cell growth compared with untreated BM MSCs. Collectively, our data show that increased frequency of IL-22 C IL-17 ¡ IL-13 C T cells correlates with poor prognosis in MM through IL-22 and IL-13 protumor activity and suggest that interference with IL-22 and IL-13 signaling pathways could be exploited for therapeutic intervention.

show abstract

“…The former is illustrated by a hazard ratio of 2.2 for developing infections even in patients with the MM precursor disease monoclonal gammopathy of unknown significance (MGUS) [8], the latter by an excess risk for malignancies such as non-melanoma skin cancer or acute myeloid leukemia/myelodysplastic syndrome in MM patients [9]. Malfunction of components of the innate and adoptive immune system in MM patients has also been described [10–12]. In addition, MM cells can specifically shield themselves from T cell responses by overexpressing protective molecules such as PD-L1, especially in the context of inflammatory cytokines [13].…”

Section: Immunotherapy Of MM – a Long Journey To Successmentioning

confidence: 99%

Immunologic approaches for the treatment of multiple myeloma

Rasche

Weinhold

Morgan

et al. 2017

Cancer Treatment Reviews

View full text Add to dashboard Cite

The FDA approval of two monoclonal antibodies in 2015 has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, ‘off-target’ immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies. We also describe some of the limitations of the current strategies and speculate on the future of personalized immunotherapies for MM.

show abstract

The Immune Microenvironment of Myeloma

Cited by 45 publications

References 118 publications

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival

Immunologic approaches for the treatment of multiple myeloma

Contact Info

Product

Resources

About