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Cellular and Molecular Life Sciences

, Volume 73, Issue 8, pp 1569–1589 | Cite as

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

  • Camille Guillerey
  • Kyohei Nakamura
  • Slavica Vuckovic
  • Geoffrey R. Hill
  • Mark J. SmythEmail author
Review

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.

Keywords

Multiple myeloma Tumor microenvironment Immune responses Immune escape Immunotherapy 

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

Notes

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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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Camille Guillerey
    • 1
    • 2
  • Kyohei Nakamura
    • 1
  • Slavica Vuckovic
    • 2
    • 3
  • Geoffrey R. Hill
    • 3
  • Mark J. Smyth
    • 1
    • 2
    Email author
  1. 1.Immunology of Cancer and Infection LaboratoryQIMR Berghofer Medical Research InstituteHerstonAustralia
  2. 2.School of MedicineThe University of QueenslandHerstonAustralia
  3. 3.Bone Marrow Transplantation LaboratoryQIMR Berghofer Medical Research InstituteHerstonAustralia

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