Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17‐1A

Abstract

Tumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17-1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies. Between 1986 and 1998, 73 patients were treated with regimens containing MAb17-1A. Prior to therapy, the lytic capability of PBMC was assayed against: K562 (4 hr assay), the CRC cell line SW948 (4 hr and 18 hr assays) and antibody-dependent cellular cytotoxicity (ADCC, 18 hr assay). Since the study was performed over 13 years, the assays were checked for time-related bias. Reproducibility over time was satisfactory. Patients exhibited a significantly higher cytotoxic capability in all 4 assays compared to healthy control donors. No correlation to clinical outcome was noted for 18 hr ADCC and 18 hr spontaneous cytotoxicity. Pretreatment natural killer (NK) cell cytotoxicity (K562) was significantly related to overall survival (OS), progression-free survival (PFS), and response rate. OS for patients with high and low NK cell cytotoxicity was 71 vs. 30 weeks, respectively (p ‫؍‬ 0.007). NK cell cytotoxicity (K562) was an independent prognostic factor for OS (p ‫؍‬ 0.016). Pretreatment NK cell activity is a strong prognostic factor for patients with metastatic CRC receiving MAb17-1A therapy and is a predictor for OS, PFS and response. These results should be considered when designing antibody-based therapeutic protocols.

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer

“…Of particular importance, patients in that study were stratified into those with high versus low NKCA and overall survival for patients was 71 weeks versus 30 weeks, respectively. Further, NKCA was an independent prognostic factor for overall survival in that study (Liljefors et al, 2003). It is worth noting that breast cancer cells can express relatively little or no HLA (Redondo, et al, 2003;Zia, et al, 2001).…”

“…The clinical significance of immune modulation during cancer is supported in several ways. High levels of NKCA in cancer patients correlate with a good prognosis (Gonzales, et al, 1998;Koda, et al, 1997;Liljefors, et al, 2003;Nakamura, et al, 2000;Seo and Tokura, 1999;Taketomi, et al, 1998). Impaired NKCA correlates with invasiveness of human malignancy (Levy, et al, 1984) and reduced NKCA is a significant prognostic indicator of lymphatic involvement, serosal invasion, lymph node metastatic disease and a poorer survival rate (Takeuchi, et al, 2001).…”

Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1,2 dimethylhydrazine (DMH)

“…This hypothesis has yet to be confirmed in future experimental studies searching for an optimal dose of cytokines, as the potential activity of IL-12 together with IL-2 continues to be an attractive option. In this way, recent studies (32,33) are going to open up new options in the selection of patients for immune treatments, where not only the stimulation of a number of intratumor infiltrates of NK cells, but also the antineoplastic activity of this kind of cells in vitro should be considered (34,35). Nevertheless, we think that the tumor model used is a useful model for antitumor treatment trials, as was the case with our study of intestinal cancer.…”

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

“…In contrast, increased NK-cell numbers and NK activity have also been reported in breast cancer and colon cancer before neo-adjuvant immunotherapy and correlated to time to treatment failure (Nicolini et al, 1996;Murta et al, 2000;Liljefors et al, 2003). Abnormalities in expression of activation molecules such as TCR , ZAP70 and p56 lck protein expression using western blot in BC (Kurt et al, 1998) as well as impaired expression of interferon-g (IFN-g) in BC and lung cancer using enzyme-linked immunosorbent assay (Caras et al, 2004) have been described.…”