Elevated IL-17 Produced by TH17 Cells Promotes Myeloma Cell Growth and Inhibits Immune Function in Multiple Myeloma

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2010 Apr 17

PMID 20395418

Citations 190

Authors

Rao H Prabhala

Dheeraj Pelluru

Mariateresa Fulciniti

Harsha K Prabhala

Puru Nanjappa

Weihua Song

Christine Pai

Samir Amin

Yu-Tzu Tai

Paul G Richardson

Irene M Ghobrial

Steven P Treon

John F Daley

Kenneth C Anderson

Jeffery L Kutok

Nikhil C Munshi

Affiliations

Soon will be listed here.

Abstract

Elevated cytokines in bone marrow (BM) micro-environment (interleukin-6 [IL-6], transforming growth factor-beta [TGF-beta], and IL-1beta) may play an important role in observed immune dysfunction in multiple myeloma (MM). As IL-6 and TGF-beta are important for the generation of T-helper 17 (T(H)17) cells, we evaluated and observed a significantly elevated baseline and induced frequency of T(h)17 cells in peripheral blood mononuclear cells (PBMCs) and BM mononuclear cells (BMMCs) from MM patients compared with healthy donors. We observed significant increase in levels of serum IL-17, IL-21, IL-22, and IL-23 in blood and BM in MM compared with healthy donors. We also observed that myeloma PBMCs after T(H)17 polarization significantly induced IL-1alpha, IL-13, IL-17, and IL-23 production compared with healthy donor PBMCs. We next observed that IL-17 promotes myeloma cell growth and colony formation via IL-17 receptor, adhesion to bone marrow stromal cells (BMSCs) as well as increased growth in vivo in murine xenograft model of human MM. Additionally, we have observed that combination of IL-17 and IL-22 significantly inhibited the production of T(H)1-mediated cytokines, including interferon-gamma (IFN-gamma), by healthy donor PBMCs. In conclusion, IL-17-producing T(h)17 cells play an important role in MM pathobiology and may be an important therapeutic target for anti-MM activity and to improve immune function.

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