Brenner B G, Margolese R G
Department of Surgical Oncology, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
Cancer. 1991 Aug 1;68(3):482-8. doi: 10.1002/1097-0142(19910801)68:3<482::aid-cncr2820680306>3.0.co;2-9.
Peripheral blood natural killer (NK) activity against K562 target tumor cells was monitored in patients with breast cancer receiving no treatment, combination chemotherapy, and/or endocrine therapy. NK activity in untreated Stage I patients with no evidence of disease (ned) was significantly higher than in healthy controls. NK activity was shown to decline in individuals with cytotoxic drug therapy (P equals 0.036). There also were reduction in lymphocyte recoveries concomitant with chemotherapeutic intervention (P less than 0.001). Lymphocyte counts were incorporated in a calculation of absolute NK activity that more accurately reflected the significant reduction in NK activity that occurred in patients with localized and systemic disease on chemotherapy. Different chemotherapeutic agents were found to selectively affect NK activity. Stage II patients on phenylalanine mustard (P)/5-fluorouracil (F) (PF) and cyclophosphamide (C)/methotrexate (M)/5-fluorouracil (F) (CMF) protocols showed significant reductions in overall NK activity relative to healthy controls and Stage I patients with ned. Patients on P/doxorubicin (A)/F/tamoxifen (Tx) (PAFT) protocols showed reduced NK activity relative to Stage I patients. Patients on the short-dose C/A (CA) protocol showed normal levels of overall NK activity. High-risk Stage I patients on methotrexate (M)/F (MF)with sequential leucovorin rescue and patients with metastatic disease on endocrine therapy, i.e., Tx or megestrol acetate (Meg) showed overall NK activities in the range of healthy controls. Patients with systemic disease on CMF, CMF/vincristine/prednisone (CMFVP), vinblastine/A/thiotepa/fluoxymesterone (VATH), mitomycin/mitoxantrone (MtMx), and A regimens showed overall levels of absolute NK that were significantly less than either healthy controls or metastatic patients undergoing endocrine therapy. NK cytolytic data, monitored at multiple effector to target ratios, were subjected to exponential regression analysis. The elevation of NK cell responses in Stage I patients with ned and the decline of NK cell responses with cytotoxic chemotherapy were due to alterations in the maximal plateau levels of NK cell cytotoxicity represented by the A (asymptote) values. The k values obtained on regression analysis and indices of the relative killing capacities of individual NK cells remained unaltered in all populations. These results suggest that the cytolytic lymphocyte NK pool, elevated in Stage I patients with cancer, selectively declines as a result of cytotoxic therapy.
对未接受治疗、接受联合化疗和/或内分泌治疗的乳腺癌患者，监测其外周血自然杀伤（NK）细胞对K562靶肿瘤细胞的活性。无疾病证据（ned）的未经治疗的I期患者的NK活性显著高于健康对照。细胞毒性药物治疗的个体NK活性下降（P = 0.036）。化疗干预时淋巴细胞恢复也减少（P < 0.001）。淋巴细胞计数被纳入绝对NK活性的计算中，该计算更准确地反映了化疗时局部和全身性疾病患者NK活性的显著降低。发现不同的化疗药物对NK活性有选择性影响。接受苯丙氨酸氮芥（P）/5-氟尿嘧啶（F）（PF）和环磷酰胺（C）/甲氨蝶呤（M）/5-氟尿嘧啶（F）（CMF）方案治疗的II期患者相对于健康对照和无疾病证据的I期患者，总体NK活性显著降低。接受P/阿霉素（A）/F/他莫昔芬（Tx）（PAFT）方案治疗的患者相对于I期患者NK活性降低。接受短疗程C/A（CA）方案治疗的患者总体NK活性水平正常。接受甲氨蝶呤（M）/F（MF）序贯亚叶酸解救的高危I期患者和接受内分泌治疗（即Tx或醋酸甲地孕酮（Meg））的转移性疾病患者的总体NK活性在健康对照范围内。接受CMF、CMF/长春新碱/泼尼松（CMFVP）、长春碱/A/噻替派/氟甲睾酮（VATH）、丝裂霉素/米托蒽醌（MtMx）和A方案治疗系统性疾病的患者的绝对NK总体水平显著低于健康对照或接受内分泌治疗的转移性患者。在多个效应细胞与靶细胞比例下监测的NK细胞溶解数据进行指数回归分析。无疾病证据的I期患者NK细胞反应的升高和细胞毒性化疗时NK细胞反应的下降是由于以A（渐近线）值表示的NK细胞细胞毒性最大平台水平的改变。回归分析获得的k值和单个NK细胞相对杀伤能力的指数在所有群体中均保持不变。这些结果表明，癌症I期患者中升高的细胞溶解淋巴细胞NK库由于细胞毒性治疗而选择性下降。
