The T Cell in Myeloma.
An active role for the immune system in controlling the malignant plasma cell clone in myeloma has been postulated for many years. The clinical states of monoclonal gammopathy of undetermined significance, plateau phase disease, and smoldering myeloma all suggest that a significant host-tumor interaction is taking place. The fundamental role of the cytotoxic T cell in tumor elimination and control has been exemplified by the dramatic efficacy of adoptive T-cell therapies in many hemopoietic malignancies. However, tumor-host cross-talk results in suppression of the endogenous cytotoxic T-cell response against the malignant plasma cell. Whereas patients with myeloma do not clinically exhibit a T-cell immunodeficiency state, with, for example, increased mycobacterial infections, a number of abnormalities of T-cell function are evident. The major abnormalities of T cells include clonal expansions and associated immunosenescence, alterations of regulatory T cells/T helper 17 cells (Treg/Th17 ratio) and acquired membrane abnormalities, due to trogocytosis, which result in acquired Treg cells. Dendritic cell dysfunction associated with impaired antigen processing and presentation caused by abnormalities of the bone marrow microenvironment plays an additional role. In this perspective, we examine the T-cell abnormalities in myeloma and postulate that, whereas cytotoxic T cells interacting with the tumor are dysfunctional, residual T cells still function adequately against external pathogens and thus protect patients from the infections normally associated with a generalized T-cell immunodeficiency state. The so-called 3 E's of host-tumor interaction (elimination, equilibrium, and escape) are clearly reflected in the immune landscape and clinical behavior of myeloma.
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia. Electronic address: douglas.joshua@sswahs.nsw.gov.au.
Douglas
D
Joshua
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
Hayley
H
Suen
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
Ross
R
Brown
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia; Dendritic Cell Research, ANZAC Research Institute, University of Sydney, Concord, NSW, Australia.
Christian
C
Bryant
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
P Joy
PJ
Ho
Dendritic Cell Research, ANZAC Research Institute, University of Sydney, Concord, NSW, Australia.
Derek
D
Hart
Institute of Haematology, NSW Pathology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
John
J
Gibson
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002450:Cell Communication / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D060965:Clonal Evolution; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D000970:Antineoplastic Agents
Clonal T-cell expansions; Immunosenescence; Multiple myeloma; Treg/Th17 ratio; Trogocytosis