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Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival
- Source :
- Oncoimmunology
- Publication Year :
- 2015
-
Abstract
- 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+IL-17-IL-13+ 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+CXCR4+CCR4+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 [IFNγ], 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+IL-17-IL-13+ 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.
- Subjects :
- Cellular differentiation
Immunology
Biology
interleukin-13
CXCR4
Ab, antibody
BM, bone marrow
BMMCs, bone marrow mononuclear cells
DCs, dendritic cells
Dx, dexamethasone
ICS, intracellular cytokine staining
IFN, interferon
IL, interleukin
ISS, International Staging System
LCL, Epstein–Barr virus-transformed B lymphoblastoid cell line
Ln, lenalidomide
MGUS, monoclonal gammopathy of undetermined clinical significance
MM, multiple myeloma
MSC, mesenchymal stromal cell
PB, peripheral blood
PBMCs, peripheral blood mononuclear cells
pDCs, plasmacytoid dendritic cells
SMM, smoldering multiple myeloma
Th, T helper
TNF, tumor necrosis factor
Treg, regulatory T cells
WB, Western blot
medicine
Immunology and Allergy
Th22 cell
Interferon gamma
Original Research
Th22 cells
bone marrow microenvironment
IL-22RA1
Cell growth
interleukin-22
Mesenchymal stem cell
bone marrow mesenchymal stromal cells
multiple myeloma
medicine.anatomical_structure
Oncology
Cell culture
Interleukin 13
Cancer research
Bone marrow
CD4+ T helper lymphocytes
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Oncoimmunology
- Accession number :
- edsair.doi.dedup.....808e117e56001cea1c47bc83bc8284fd