Skip to main content Accessibility help
×
Hostname: page-component-68c7f8b79f-wfgm8 Total loading time: 0 Render date: 2025-12-28T22:08:34.408Z Has data issue: false hasContentIssue false

7 - Immune dysfunction in multiple myeloma

from Section 2 - Biological basis for targeted therapies in myeloma

Published online by Cambridge University Press:  18 December 2013

By
Guy Pratt  and
Paul Moss
Edited by
Stephen A. Schey ,
Kwee L. Yong ,
Robert Marcus  and
Kenneth C. Anderson
Stephen A. Schey
Affiliation:
Department of Haematology, King’s College Hospital, London
Kwee L. Yong
Affiliation:
Department of Haematology, University College Hospital, London
Robert Marcus
Affiliation:
Department of Haematology, King’s College Hospital, London
Kenneth C. Anderson
Affiliation:
Dana-Farber Cancer Institute, Boston
Get access

Summary

Introduction

Immune dysfunction is an important feature of multiple myeloma and infection remains a major cause of morbidity and mortality. Numerous defects of the immune system occur in multiple myeloma and can also be observed in monoclonal gammopathy of uncertain significance. Indeed, evidence suggests that immune deficiency and infection may serve to promote progression to MM.

There has also been considerable interest in the identification of an autologous response against myeloma. Although cellular and humoral responses directed against myeloma-associated antigens have been described, it remains somewhat uncertain if the immune system plays a significant role in preventing or controlling myeloma cell growth. Despite this, there is an increasing interest in the potential role of immunotherapeutic approaches to treatment paraproteinemia although the immunologically hostile environment associated with multiple myeloma remains a major challenge.

An improved understanding of the mechanisms that mediate immune surveillance and tumor immunity in myeloma are important as a basis for improving patient outcome and are the subject of this review (Table 7.1).

Information

Type
Chapter
Information
Myeloma
Pathology, Diagnosis, and Treatment
 , pp. 84 - 95
Publisher: Cambridge University Press
Print publication year: 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Augustson, B. M., Begum, G., Dunn, J. A., et al. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002–Medical Research Council Adult Leukaemia Working Party. J. Clin. Oncol. 2005;23:9219–26.CrossRefGoogle Scholar
Rayner, H. C., Haynes, A. P., Thompson, J. R., Russell, N., Fletcher, J.Perspectives in multiple myeloma: survival, prognostic factors and disease complications in a single centre between 1975 and 1988. Quarterly J. Med. 1991;79:517–25.Google Scholar
Oken, M., Pomeroy, C., Weisdorf, D., Bennett, J.Prophylactic antibiotics for the prevention of early infection in multiple myeloma. Am. J. Med. 1996;100:624–8.CrossRefGoogle ScholarPubMed
Vesole, D. H., Oken, M. M., Heckler, C. et al. Oral antibiotic prophylaxis of early infection in multiple myeloma: a URCC/ECOG Phase III study. Blood 2010;116 (abstract 3017).Google Scholar
Raanani, P., Gafter-Gvili, A., Paul, M. et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk. Lymphoma 2009;50:764–72.CrossRefGoogle ScholarPubMed
Chiron, D., Jego, G., Pallat-Deuceunynck, C.Toll-like receptors: expression and involvement in multiple myeloma. Leuk. Res. 2010;34:1545–50.CrossRefGoogle ScholarPubMed
Landgren, O., Rapkin, J. S., Mellemkjaer, L. et al. Respiratory tract infections in the pathway to multiple myeloma: a population-based study in Scandinavia. Haematologica 2006;91:1697–700.Google ScholarPubMed
Kristinsson, S. Y., Bjorkholm, M., Andersson, T. M. et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population based study. Haematologica 2009;94:1641–4.CrossRefGoogle ScholarPubMed
Ratta, M., Fagnoni, F., Curti, A. et al. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 2002;100:230–7.CrossRefGoogle ScholarPubMed
Kay, N. E., Leong, T. L., Bone, N. et al. Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients. Blood 2001;98:23–8.CrossRefGoogle ScholarPubMed
Chauhan, D., Singh, A. V., Brahmandam, M. et al. Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell 2009;16:309–23.CrossRefGoogle ScholarPubMed
Moss, P., Gillespie, G., Frodsham, P., Bell, J., Reyburn, H.Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia. Blood 1996;87:3297–306.Google ScholarPubMed
Thompson, K., Rojas-Navea, J., Rogers, M. J.Alkylamines cause Vgamma9Vdelta2 T-cell activation and proliferation by inhibiting the mevalonate pathway. Blood 2006;107:651–4.CrossRefGoogle ScholarPubMed
Girlanda, S., Fortis, C., Belloni, D. et al. MICA expressed by multiple myeloma and monoclonal gammopathy of undetermined significance plasma cells costimulates pamidronate-activated gammadelta lymphocytes. Cancer Res. 2005;65:7502–8.CrossRefGoogle ScholarPubMed
Beyer, M., Kochanek, M., Giese, T., et al. In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood 2006;107:3940–9.CrossRefGoogle ScholarPubMed
Feyler, S., von Lilienfeld-Toal, M., Jarmin, S., et al. CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(-)CD8(-)alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden. Br. J. Haematol. 2009;144;686–95.CrossRefGoogle ScholarPubMed
Prabhala, R. H., Neri, P., Bae, J. E. et al. Dysfunctional T regulatory cells in multiple myeloma. Blood 2006;107:301–4.CrossRefGoogle Scholar
Noonan, K., Marchionni, L., Anderson, J. et al. A novel role of IL-17 producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 2010;116:3554–63.CrossRefGoogle ScholarPubMed
Dhodapkar, K. M., Barbuto, S., Matthews, P. et al. Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17–1 cells) enriched in the bone marrow of patients with myeloma. Blood 2008;112:2878–85.CrossRefGoogle ScholarPubMed
Prabhala, R. H., Pelluru, D., Fulciniti, M. et al. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010;115:5385–92.CrossRefGoogle ScholarPubMed
Carbone, E., Neri, P., Mesuraca, M. et al. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood 2005;105:251–8.CrossRefGoogle Scholar
Davies, F. E., Raje, N., Hideshima, T. et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210–16.CrossRefGoogle ScholarPubMed
Bernal, M., Garrido, P., Jiménez, P. et al. Changes in activatory and inhibitory natural killer (NK) receptors may induce progression to multiple myeloma: implications for tumor evasion of T and NK cells. Hum. Immunol. 2009;70;854–7.CrossRefGoogle Scholar
Benson, D. M., Bakan, C. E., Mishra, A. et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 2010;11:2286–94.CrossRefGoogle Scholar
Dhodapkar, M. V., Geller, M. D., Chang, D. H. et al. A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma. J. Exp. Med. 2003;198:1667–76.CrossRefGoogle Scholar
Yi, Q., Dabadghao, S., Osterborg, A., Bergenbrant, S., Holm, G.Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells. Blood 1997;90:1960–7.Google ScholarPubMed
Racanelli, V., Leone, P., Frassanito, M. A. et al. Alterations in the antigen processing-presenting machinery of transformed plasma cells are associated with reduced recognition by CD8+ T cells and characterize the progression of MGUS to multiple myeloma. Blood 2010;115:1185–93.CrossRefGoogle Scholar
Lu, Z. Y., Condomines, M., Tarte, K. et al. B7–1 and 4–1BB ligand expression on a myeloma cell line makes it possible to expand autologous tumor-specific cytotoxic T cells in vitro. Exp. Hematol. 2007;35:443–53.CrossRefGoogle ScholarPubMed
Goodyear, O., Pratt, G., McLarnon, A. et al. Differential pattern of CD4+ and CD8+ T cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Blood 2008;112:3362–72.CrossRefGoogle ScholarPubMed
van Rhee, F., Szmania, S. M., Zhan, F. et al. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood 2005;105:3939–44.CrossRefGoogle ScholarPubMed
Yi, Q., Osterborg, A., Bergenbrant, S. et al. Idiotype-reactive T-cell subsets and tumor load in monoclonal gammopathies. Blood 1995;86:3043–9.Google ScholarPubMed
Michalek, J., Ocadlikova, D., Matejkova, E. et al. Individual myeloma-specific T-cell clones eliminate tumour cells and correlate with clinical outcomes in patients with multiple myeloma. Br. J. Haematol. 2010;148:859–67.CrossRefGoogle ScholarPubMed
Jungbluth, A. A., Ely, S., DiLiberto, M. et al. The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation. Blood 2005;106:167–74.CrossRefGoogle ScholarPubMed
Atanackovic, D., Arfsten, J., Cao, Y. et al. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood 2007;109:1103–12.CrossRefGoogle ScholarPubMed
Hong, S., Qian, J., Yang, J. et al. Roles of idiotype-specific t cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth. Cancer Res. 2008;68:8456–64.CrossRefGoogle ScholarPubMed
Dhodapkar, M. V., Krasovsky, J., Osman, K., Geller, M. D.Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. J. Exp. Med. 2003;198:1753–7.CrossRefGoogle ScholarPubMed
Blotta, S., Tassone, P., Prabhala, R. H. et al. Identification of novel antigens with induced immune response in monoclonal gammopathy of undetermined significance. Blood 2009;114:3276–384.CrossRefGoogle ScholarPubMed
Spisek, R., Kukreja, A., Chen, L. C. et al. Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. J. Exp. Med. 2007;204:831–40.CrossRefGoogle ScholarPubMed
Pérez-Andrés, M., Almeida, J., Martín-Ayuso, M. et al. Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment. Leukemia 2005;19:449–55.CrossRefGoogle ScholarPubMed
Jinushi, M., Vanneman, M., Munshi, N. C. et al. MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma. Proc. Natl Acad. Sci. USA 2008;105:1285–90.CrossRefGoogle ScholarPubMed
Gorgun, G., Calabrese, E., Soydan, E. et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2010;116:3227–37.CrossRefGoogle ScholarPubMed
Xu, Y., Li, J., Ferguson, G. D. et al. Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood 2009;114:338–45.CrossRefGoogle ScholarPubMed
Hsu, A. K., Quach, H., Tai, T. et al. The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood 2011;117:1605–13.CrossRefGoogle ScholarPubMed
Nencioni, A., Grunebach, F., Patrone, F., Ballestro, A., Brossart, P.Proteasome inhibitors: antitumor effects and beyond. Leukemia 2007;21:30–6.CrossRefGoogle ScholarPubMed
Luckey, C. J., Marto, J. A., Partridge, M. et al. Differences in the expression of human class I MHC alleles and their associated peptides in the presence of proteasome inhibitors. J. Immunol. 2001;167:1212–21.CrossRefGoogle ScholarPubMed
Crawley, C., Iacobelli, S., Bjorkstrand, B. et al. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007;109:3588–94.CrossRefGoogle ScholarPubMed
Gahrton, G., Svensson, H., Bjorkstand, B. et al. Syngeneic transplantation in multiple myeloma – a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1999;24:741–5.CrossRefGoogle ScholarPubMed
Rosenblatt, J., Vasir, B., Uhl, L. et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood 2011;117:393–402.CrossRefGoogle ScholarPubMed
Rapoport, A. P., Aqui, N. A., Stadtmauer, E. A. et al. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 2011;117:788–97.CrossRefGoogle ScholarPubMed
Rapoport, A. P., Stadtmauer, E. A., Aqui, N. et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nature Med. 2005;11:1230–7.CrossRefGoogle ScholarPubMed

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×