TY - JOUR
T1 - Multiple myeloma cells express key immunoregulatory cytokines and modulate the monocyte migratory response
AU - Freire-de-Lima, Leonardo
AU - Nardy, Ana Flávia Fernandes Ribas
AU - Ramos-Junior, Erivan Schnaider
AU - Conde, Luciana
AU - Santos Lemos, Jéssica
AU - da Fonseca, Leonardo Marques
AU - Lima, Juliana Echevarria
AU - Maiolino, Angelo
AU - Morrot, Alexandre
N1 - Funding Information:
This work was supported by grants from Fundação do Câncer, Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).
Publisher Copyright:
2017 Freire-de-Lima, Nardy, Ramos-Junior, Conde, Santos Lemos, Fonseca, Lima, Maiolino and Morrot.
PY - 2017/6/27
Y1 - 2017/6/27
N2 - 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-ϒ 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.
AB - 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-ϒ 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.
KW - Immune response
KW - Immunoregulation
KW - Leukocyte migration
KW - Monocytes
KW - Multiple myeloma
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U2 - 10.3389/fmed.2017.00092
DO - 10.3389/fmed.2017.00092
M3 - Article
AN - SCOPUS:85037983360
SN - 2095-0217
VL - 4
JO - Frontiers of Medicine
JF - Frontiers of Medicine
M1 - 92
ER -