Immune suppression in BALB/c mice bearing the plasmacytoma TEPC‐183: Evidence for normal lymphocyte but defective macrophage function

Abstract

This paper analyses impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy animals and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The defect was shown to affect both primary IgG and IgM responses to chicken cells (CRBC) and to be related to tumour size. However, the primary immune depression could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Secondary responses were also depressed. This depression was more pronounced if the animals was primed after, rather than before, tumour implantation. Further studies involved the measurement of primary immune responses of immunologically deprived syngeneic mice, after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950R. Various lymphoid preparations from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage, rather than a lymphocyte, abnormality. However, none of these transfer studies suggested that positive suppression of primary immune responses was being mediated by cells from TEPC-183-bearing mice.

Either interleukin‐12 or interferon‐γ can correct the dendritic cell defect induced by transforming growth factor β1 in patients with myeloma

“…Other studies have demonstrated a reversible defect in the natural killer cells of patients with MM (Dhodapkar et al , 2003). Early murine studies suggested that the poor immune response was due to a defect in antigen‐presenting cells (Joshua et al , 1979) and more recently a defect in the DC of patients with MM has been defined by our group and others (Brown et al , 2001; Ratta et al , 2002). Thus, the poor response to idiotype vaccination and other active immunotherapy strategies in these patients (Ruffini et al , 2002) should have been expected.…”

Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-β1 and interleukin-10

“…However, patients with myeloma respond poorly to immunization by viral and bacterial antigens, 7 and murine studies have suggested that this defect is associated with APCs rather than with T cells. 8 It is, therefore, not surprising that idiotype vaccination trials have had little success. Clearly, more careful consideration of the biology of host-tumor interactions, including an understanding of the induction of T-cell tolerance by tumor antigens and a characterization of the dysfunction of APCs in patients with myeloma, is required before more effective immunotherapy schedules can be developed.…”

“…7 Murine studies have suggested that this defect is associated with antigen presenting cells (APCs). 8 There have been reports that the DCs of patients with myeloma are functionally normal 9,10 ; however, the criteria used to define DCs in these latter studies included monocytes-macrophages and even B cells. Preliminary reports of immunotherapy trials in patients with myeloma have demonstrated only minor responses.…”

Light chain isotype‐associated suppression of normal plasma cell numbers in patients with multiple myeloma

“…Several theories have been postulated from experimental work in human and animal B-cell neoplasia to explain the mechanism or mechanisms of secondary hypogammaglobulinaemia. These include: hypercatabolism of antibody (Lippincott et al, 1960;Solomon et al, 1963); increased action of suppressor cells (Broder er al., 1975;Krakauer et al, 1977;Kolb et al, 1977); B-cell inactivation by tumour RNA (Heller et al, 1973) and defective antigen processing (Joshua et al, 1979). This variety of postulated mechanisms may in part reflect differences in the types of B-cell tumour studied.…”