Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study

Abstract

Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.

Immune dysfunction and micrometastases in women with breast cancer

“…This technique enables the characterization of both phenotype (CD4 and CD8) and function (type of cytokine produced) of T cells at the single-cell level. Cell mediated immunity in breast cancer patients has been evaluated by various assays including proliferation and cytotoxicity assays [22][23][24][25][26][27]. Immunological dysfunction has been reported in some cases, but the results have sometimes been equivocal or confounded by other factors such as prior chemotherapy or radiotherapy.…”

Immune functions, clinical parameters and hormone receptor status in breast cancer patients

“…With regard to the T lymphocyte responses, Wiltscheke et al (1995) have reported poor proliferation of peripheral blood mononuclear cells in response to PHA in breast cancer patients, the degree of defect being directly correlated to stage of the disease, including tumour size and lymph node status.…”

“…The extent of impairment of immune functions in patients was further highlighted by the v 2 -test (Table 4), which showed signi®cant dierences in the numbers of low responders in breast cancer patients and controls with regard to NK cell function (P = 0.025), CD3-directed lysis (P = 0.043) and proliferative response to PHA in terms of stimulation index (P = 0.001) or the magnitude of response, D 3 H (P = 0.016). In the past several researchers (reviewed in Trinchieri 1989;Wiltscheke et al 1995) have proposed the possible use of NK and T cell function studies as prognostic markers, though the definition of poor responders has varied. Our approach of identifying low responders with stringent cut-o values for each parameter may be better if their use as prognostic markers is considered.…”

“…Earlier studies have shown that breast cancer patients exhibit a lower T cell function, demonstrated as an impaired proliferative response to phytohaemagglutinin (PHA) correlating with the stage of the disease and the tumour burden (Wiltscheke et al 1995). In another study an association of impaired T lymphocyte functional competence with pathological nodal status, with no relation to tumour burden, extension to skin/muscle or metastasis was demonstrated.…”

Monitoring of Intracellular Enzyme Kinetic Characteristics of Peripheral Mononuclear Cells in Breast Cancer Patients

“…The modifications of the total activity of esterases in tumor cells, as well as in the peripheral mononuclear cells, may be related to impairment of protein carbamoylation and the consequent changes in the processes of cellular growth and proliferation (36 -38). It seems possible that carbamoylation-related alterations of macromolecular synthesis in carcinogenesis may lead to the perturbed state of tumor-associated cells and circulating lymphocytes, as well as to a change in receptor expression, suppression of PBMC immune response, and, finally, to the detrimental effects of tumor on the regulatory systems (10,32,35,39,40). Additionally, the contravention of carbamoylation process may result, for example, in a change of the cytostatic drug toxic effects (41,42).…”