Abstract
Multiple myeloma (MM) is a plasma cell disorder that still remains incurable. The immune dysfunction of the host is a striking characteristic of MM, leading to tumor growth and reducing the survival rate of patients. Monocytes are precursors of conventional dendritic cells (DCs), a major player in the immunity mechanisms driving protective T cell responses against tumor. Herein, we report that human MM RPMI 8226 cell line shows a pronounced chemoattractant activity for monocytes and also expresses enhanced levels of the leukocyte chemotactic cytokines CXCL12, CCL5, MIP-1β, and CXCL10 in association with elevated levels of both key immunoregulatory interleukins such as IL-4 and IL-10. This cytokine profile was observed together with reduced expression of IFN-γ by MM RPMI 8226 cell line, a determinant interleukin involved in the acquisition of cellular-mediated protective responses against tumor cells. We further demonstrate that MM RPMI 8226 cell line expresses elevated levels of soluble form of the intercellular adhesion molecule-1 known to inhibit antitumoral T cell responses. This attractive modulation of immune responses by MM cells might provide a means to impair early antitumor responses during the establishment of cytokine-mediated immunosuppressive tumor niche.
Highlights
Multiple myeloma (MM) is a B-cell malignancy resulting from aberrant clonal expansion of plasma cells that initiates in the bone marrow (BM); this accounts for approximately 10% of all hematological cancers [1]
Due to the crucial role played by dendritic cells (DCs) in tumor immunity, through the initiation of adaptive immune responses mediated by T lymphocytes, we sought to investigate the ability of MM cells to potentially affect the initial stages of DC differentiation, by altering the biological process of their monocytic precursors
The direct relation between MM cells and BM microenvironment, through cell-to-cell contact and soluble factors provided by bone marrow stromal cells (BMSCs), plays a vital role in the pathogenesis of disease
Summary
Multiple myeloma (MM) is a B-cell malignancy resulting from aberrant clonal expansion of plasma cells that initiates in the bone marrow (BM); this accounts for approximately 10% of all hematological cancers [1]. Cell-to-cell contact and soluble factors provided by bone marrow stromal cells (BMSCs) play an essential role in the proliferation and survival of malignant plasma cells, contributing to the pathogenesis of the disease [2]. During the development of malignancy, MM cells alter BM microenvironment by modulating the proliferation of mesenchymal stroma cells and establishing a tumor niche [3]. The cellular mechanisms involved in the progression of myeloma disease include the contribution of different populations of myeloid cells [4]. The composition and activation of the myeloid cells are finely controlled in the formation of the MM BM niche. It has been shown that during growth of MM cells in the BM, there is an upregulation
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