Immunomodulatory Effects of Lenalidomide and Pomalidomide on Interaction of Tumor and Bone Marrow Accessory Cells in Multiple Myeloma

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2010 Jul 24

PMID 20651070

Citations 116

Authors

Gullu Gorgun

Elisabetta Calabrese

Ender Soydan

Teru Hideshima

Giulia Perrone

Madhavi Bandi

Diana Cirstea

Loredana Santo

Yiguo Hu

Yu-Tzu Tai

Sabikun Nahar

Naoya Mimura

Claire Fabre

Noopur Raje

Nikhil Munshi

Paul Richardson

Kenneth C Anderson

Affiliations

Soon will be listed here.

Abstract

The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferonγ, and IL-6 regulator suppressor of cytokine signaling (SOCS)1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1 expression in effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression. SOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing-MM cells than unmodified MM cells. These data therefore demonstrate that modulation of SOCS1 may enhance immune response and efficacy of IMiDs in MM.

Citing Articles

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