NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy

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 agematched 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.

Evaluation of T- Regulatory Cells in Breast Cancer.

“…In our study, CD4+CD25hi subset was higher in the after-surgery patients compared to the de novo patients (P=0.04) and this was in accordance with the finding of Mozaffari et al (2007).…”

Resistance of CD45RA− T Cells to Apoptosis and Functional Impairment, and Activation of Tumor-Antigen Specific T Cells during Radiation Therapy of Prostate Cancer

“…Although previous studies reported a negative effect of RT on T cell function, tested mainly by mitogeninduced proliferation assays (8,10,11), the changes in Ag-specific T cell responses during RT have been less well studied. We believe this question is especially important, as preclinical studies and two clinical trials indicate that local radiotherapy does not affect vaccine-induced T cell responses in a large proportion of patients (3,22,23), an apparent contradiction.…”

“…Lymphopenia often follows local RT as observed in prostate, testicular, and gynecological cancers (7)(8)(9). The main functional effect is impaired T cell proliferation induced either by purified protein derivative, mitogens, OKT-3 Ab, or viral Ags, as observed in breast cancer patients 45 d after finishing RT, cervical cancer patients on the last day of receiving 25 fractions of pelvic RT or in patients with testicular cancer after treatment with 26 Gy, respectively (8,10,11). Because of the apparent contradiction between potential immune activation and impairment, the question of T cell survival and function during RT needs to be clarified to improve the design of combination therapies.…”

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: Long-term follow-up of a phase II study

“…One of the reasons of failure of cancer therapy is due to the fact that the immune system is compromized in Pts with advanced breast cancer (18). Such a dysfunction may appear early in the course of disease and may worsen after cancer therapy (33).…”

“…Patients with advanced breast cancer have been reported to have a variety of functional abnormalities of the immune system, which may differ in magnitude from one subject to another one and which may be related to the extent of disease (18). As a result, the immuno-inhibitory influence of the tumor might extend far beyond the tumor microenvironment and become a systemic effect, especially in Pts with advanced and metastatic disease.…”