Biology of multiple myeloma—host‐tumour interactions and immune regulation of disease activity

Abstract

Multiple myeloma is a B lineage tumour, the neoplastic cells of which secrete a monoclonal idiotypic paraprotein and have a characteristic plasma B cell surface antigen expression, i.e. CIg+ , SIg-,PCA-I +,CD6+,CD19--,CD20-,HLA-DR-,CDlO-,Tdt-.Inaddition,anantigen shared with T blasts, i.e. TIO, CD38 is also present on plasma cells. Immunoglobulin gene rearrangements of both heavy and light chains are also seen (Foon rt al., 1982; Rosen et al., 1986).Both host-tumour and tumour-host interactions occur in myeloma and may reflect immunological regulatory mechanisms. For example there is considerable evidence to show that multiple myeloma produces a unique immunodeficiency state in the host quite unlike that produced by most cancers. Thus patients with myeloma (and mice-bearing pristane induced plasmacytomas) have hypogammaglobulinaemia, an impaired primary immune response to both T-dependent and T-independent antigens, but have a a relatively preserved secondary response and normal or near normal cell-mediated immunity (Ulrich and Zolla-Pazner, 1982; Joshua et al., 1979). This immunosuppressive effect occurs at relatively low tumour loads and is believed to be a specific effect of the malignancy. The exact aetiology of this effect is unknown, but it is postulated to be due to lack of normal B cells, active immunoregulatory circuits and defects in macrophage handling of antigen. Macrophage abnormalities could either take the form of sequestrian of antigen and/or inadequate antigen presentation. For example, mice bearing the plasmacytoma TEPCl83 have an absolute increase in macrophages in the red pulp of the spleen without any change in splenic marginal zone macrophages providing a mechanism for antigen sequestration in non-antigen presenting cells. A parallel is seen in the splenic histology of experimental murine malaria where suppression of primary and secondary antibody responses similar to that seen in the murine plasmacytomas has been reported (Joshua et al., 1980). Alternatively, on the basis of in vitro data, macrophages may act as suppressor cells. These suppressor macrophages are believed to be induced by a factor secreted by plasmacytoma cells and they in turn release a second humoral substance termed 'plasmacytoma-induced macrophage substance' (PIMS), which inhibits B cell proliferation and antibody production (Katzmann, 1978).In addition to the effect the tumour has on the host's immune system, there is suggestive evidence from the murine plasmacytoma model that the host's immunological mechanisms can modulate tumour growth. Thus early work with the murine plasmacytomas MOPC 3 15 and MOPC 460 showed that idiotypic specific tumour rejection can be elicited by immunizing with the myeloma proteins (Rohrer and Lynch, 1979). In addition, antigens in tolerogenic form (Abbas and Klaus, 1977), antigen antibody complexes (Abbas and Klaus, 1978), carrier specific helper and

Interferon‐γ+ and interleukin‐2+ T cells in peripheral blood from multiple myeloma patients in relation to disease status and maintenance therapy with interferon‐α2b (intron A)

“…Although multiple myeloma (MM) remains incurable, the existence of monoclonal gammopathies of undetermined significance (MGUS) and plateau phase suggests that tumour homeostasis may exist in vivo ( Joshua, 1988). Further evidence for tumour control is provided by the observation that tumour cells can proliferate in vitro when there is no evidence of disease in vivo (Millar et al, 1988).…”

Serum Thymidine Kinase as a Marker of Disease Activity in Patients With Multiple Myeloma

“…plateau and progressive) and the chronic and blastic phases of chronic granulocytic leukemia and postulated that these phases reflect host-tumour interactions and can be separated by the above features. 13 In the classic staging system,' the parameters used to detect the emergence of aggressive disease are hemoglobin, serum calcium, creatinine, papaprotein concentration, urinary Bence Jones protein, the percentage of bone marrow plasma cells and the presence of radiologically detectable lytic bone lesions. Recent studies have revealed several new parameters which are potentially useful tools for monitoring disease progression in myeloma.…”