1. ¹Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska University Hospital, SE-17176 Stockholm, Sweden
2. ²Department of Oncology, Central Hospital, SE-72189 Västerås, Sweden
3. ³Department of Clinical Neuroscience, Osher Center for Integrative Medicine and Section of Psychology, Karolinska Institutet, SE-17177 Stockholm, Sweden
4. ⁴Department of Cancer Epidemiology, Karolinska University Hospital, SE-17176 Stockholm, Sweden
5. ⁵Centre for Clinical Research, Uppsala University, Central Hospital, SE-72189 Västerås, Sweden
6. ⁶Departments of Hematology and Oncology, Karolinska University Hospital, SE-17176 Stockholm, Sweden
7. ⁷Department of Surgery and Centre for Clinical Research, Uppsala University, Central Hospital, SE-72189 Västerås, Sweden

Correspondence: Professor H Mellstedt, Department of Oncology (Radiumhemmet), Karolinska University Hospital, Stockholm SE-17176, Sweden. E-mail: hakan.mellstedt@karolinska.se

Received 10 January 2007; Revised 15 May 2007; Accepted 15 May 2007; Published online 5 June 2007.

Abstract

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.