Mozaffari F, Lindemalm C, Choudhury A, Granstam-Björneklett H, Helander I, Lekander M, Mikaelsson E, Nilsson B, Ojutkangas M-L, Osterborg A, Bergkvist L, Mellstedt H
Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
Br J Cancer. 2007 Jul 2;97(1):105-11. doi: 10.1038/sj.bjc.6603840. Epub 2007 Jun 5.
Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions.
乳腺癌是全球女性中最常见的恶性肿瘤。针对人表皮生长因子受体2(Her2)的单克隆抗体是已确立的治疗方式,疫苗正处于乳腺癌患者的后期临床试验阶段,并且已知其通过抗体依赖性细胞毒性等机制促进肿瘤杀伤。因此,研究传统治疗策略的免疫后果变得越来越重要。在本研究中,采用功能测试和四色流式细胞术来检测术前乳腺癌患者、接受辅助放疗或辅助放化疗的患者以及年龄匹配的健康对照者体内的自然杀伤(NK)细胞功能和受体、T细胞信号转导分子以及细胞内细胞因子。术前患者的NK细胞绝对数量、NK受体密度以及功能性NK细胞毒性的体外定量均显著高于治疗后组和对照组。T细胞信号分子也呈现类似模式,与其他组相比,术前患者的NK细胞和T细胞产生的细胞因子量显著更高。结果表明,NK细胞和T细胞的功能在手术前保存良好,但在辅助治疗后下降,这可能支持早期而非晚期使用可能依赖完整免疫效应功能的免疫治疗药物,如曲妥珠单抗。