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Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies

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Abstract

Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myeloma responses. The profound immune deregulation occurring in MM patients may be involved in the transition from a premalignant to a malignant stage of the disease. In the last decades, the advent of stem cell transplantation and new therapeutic agents including proteasome inhibitors and immunoregulatory drugs has dramatically improved patient outcomes, suggesting potentially key roles for innate and adaptive immunity in disease control. Nevertheless, MM remains largely incurable for the vast majority of patients. A better understanding of the complex interplay between myeloma cells and their immune environment should pave the way for designing better immunotherapies with the potential of very long term disease control. Here, we review the immunological microenvironment in myeloma. We discuss the role of naturally arising anti-myeloma immune responses and their potential corruption in MM patients. Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM.

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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

APC:

Antigen presenting cell

APRIL:

A proliferation-inducing ligand

BAFF:

B-cell activating factor

BM:

Bone marrow

BMSC:

BM stromal cell

CAM-DR:

Cell-adhesion mediated drug resistance

CAR:

Chimeric antigen receptor

DAMPs:

Damage-associated molecular patterns

DC:

Dendritic cell

GvHD:

Graft versus host disease

GvM:

Graft-versus-myeloma

IFN:

Interferon

Ig:

Immunoglobulin

ILC:

Innate lymphoid cell

KIR:

Killer cell immunoglobulin-like receptor

LPS:

Lipopolysaccharide

mAb:

Monoclonal antibody

MDSC:

Myeloid-derived suppressor cells

MGUS:

Monoclonal gammopathy of undetermined significance

MHC:

Major histocompatibility complex

MM:

Multiple myeloma

MSC:

Mesenchymal stem cell

NK:

Natural killer

PAMPs:

Pathogen-associated molecular patterns

pDC:

Plasmacytoid DC

PBMC:

Peripheral blood mononuclear cells

RANK:

Receptor activator of NF-κB

SCID:

Severe combined immunodeficient

TAM:

Tumor-associated macrophages

TCR:

T cell receptor

TGF:

Transforming growth factor

TLR:

Toll-like receptor

TRAIL:

TNF-related apoptosis inducing ligand

Treg:

Regulatory T cell

VEGF:

Vascular endothelial growth factor

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Acknowledgments

K.N. is supported by The Naito Foundation. M. J. S. is supported by a NH&MRC Australia Fellowship (628623) and Program Grant (1013667). C.G. is supported by a NH&MRC early career fellowship (1107417).

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Authors and Affiliations

  1. Immunology of Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia

    Camille Guillerey, Kyohei Nakamura & Mark J. Smyth

  2. School of Medicine, The University of Queensland, Herston Road, Herston, QLD, 4072, Australia

    Camille Guillerey, Slavica Vuckovic & Mark J. Smyth

  3. Bone Marrow Transplantation Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia

    Slavica Vuckovic & Geoffrey R. Hill

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  1. Camille Guillerey
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  2. Kyohei Nakamura
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Guillerey, C., Nakamura, K., Vuckovic, S. et al. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell. Mol. Life Sci. 73, 1569–1589 (2016). https://doi.org/10.1007/s00018-016-2135-z

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