Wiltschke C, Krainer M, Budinsky A C, Berger A, Müller C, Zeillinger R, Speiser P, Kubista E, Eibl M, Zielinski C C
Department of Internal Medicine, University of Vienna, Austria.
Br J Cancer. 1995 Jun;71(6):1292-6. doi: 10.1038/bjc.1995.250.
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.
免疫抑制常常与恶性疾病的病程相关。在本研究中,前瞻性地评估了90例I - III期乳腺癌患者外周血单个核细胞(PBMC)对植物血凝素(PHA)促有丝分裂刺激的增殖情况。与健康对照个体的数据相比,乳腺癌患者术前PBMC的PHA诱导增殖显著降低(P < 0.001),而PBMC的PHA诱导增殖缺陷程度取决于肿瘤负荷,如肿瘤大小和腋窝淋巴结受累情况(每种情况P < 0.003)。在观察6个月后,接受由环磷酰胺、甲氨蝶呤和氟尿嘧啶(CMF)组成的辅助化疗的患者,其PBMC的PHA诱导增殖显著下降(P < 0.01),但仅接受他莫昔芬辅助治疗的患者未出现这种情况。再过6个月(即术后12个月),接受CMF辅助化疗的患者与继续接受他莫昔芬辅助治疗的患者,其PBMC的PHA诱导增殖相似(P > 0.1),但与健康对照相比,所有患者的该指标仍显著降低(P < 0.001)。比较术前和术后12个月的数据发现,在23例PBMC的PHA诱导增殖下降的患者中,有14例(61%)在随后的24个月内(即术后36个月)发生了转移疾病。相比之下,在59例术后前12个月内PBMC的PHA诱导增殖增加的患者中,只有1例(2%)出现疾病进展。因此,我们得出结论,乳腺癌患者PBMC的PHA诱导增殖取决于肿瘤负荷,是疾病进一步发展的良好临床预测指标。