Targeting the immune niche within the bone marrow microenvironment: The rise of immunotherapy in Multiple Myeloma.

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Targeting the immune niche within the bone marrow microenvironment: The rise of immunotherapy in Multiple Myeloma.

Curr Cancer Drug Targets. 2017 Feb 13;:

Authors: Podar K, Jäger D

Abstract
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance. The usefulness of immunotherapies in MM patients has first been supported by the identification of the graft-versus-myeloma effect in the context of allogeneic bone marrow (BM) transplantation. Subsequently, the inclusion of thalidomide and its derivatives, the Immunomodulatory Drugs (IMiDs) as well as of (immuno) proteasome inhibitors into MM regimens dramatically improved MM patients' outcome during the last 15 years. Despite these unprecedented therapeutic advances MM remains an incurable disease. Novel immunotherapeutic approaches aim to restore the balance within the immunologic niche of the MM BM microenvironment. Indeed, the inclusion of monoclonal antibodies, immune checkpoint inhibitors, chimeric antigen receptor-engineered (CAR) T cells, genetically engineered T cells, and vaccination, dendritic cell- based cancer vaccines in particular, into existing regimens is likely to significantly improve MM patient outcome in the near future.

PMID: 28201977 [PubMed - as supplied by publisher]

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