Effect of surgery on pancreatic tumor-dependent lymphocyte asset: modulation of natural killer cell frequency and cytotoxic function.

OBJECTIVES: Tumor burden and invasiveness establish a microenvironment that surgery could alter. This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy. METHODS: Lymphocyte frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro assay on peripheral blood from initial and advanced-stage pancreatic cancer patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery. RESULTS: An increase in natural killer (NK) cells and the diminution of B-cells occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK behavior. The elevation of NK cell frequency at PS30, an initial defect in CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity remained significant in advanced-stage patients, whereas the diminution of NK cytotoxicity only affected initial stage patients. CONCLUSIONS: The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

The interaction of tenascin-C with fibronectin modulates the migration and specific metalloprotease activity in human mesothelioma cell lines of different histotype.

Malignant mesothelioma (MM) is a tumor with local invasive behaviour. Tenascin-C (TN-C) with fibronectin (FN) are associated extracellular matrix (ECM) molecules frequently neo-expressed in stromal remodeling during neoplastic progression, mostly at the invasive edge of these tumors. Tenascin-C alone or in association with other ECM molecules, could play an important role in the process of tumor invasion, acting as substrate for movement or modulating the migration on FN or promoting the degradation of ECM. Three mesothelioma cell lines of different histotype were analysed for the adhesive capacity on TN-C. The haptotactic activity on TN and the TN modulation of migration on a substrate of FN were analysed by a Boyden modified chamber. The effects of TN on proteolytic activity was evaluated by zymography. None of the lines adhered to tenascin. TN-C was not haptotactic for the three cell lines. Soluble or solid TN reduced the migration on FN of epithelial (E-MM) and sarcomatous cell line (S-MM), whereas enhanced the movement of a byphasic cell line (B-MM). When the cells were pretreated with anti-integrin blocking antibodies we observed a different pattern of inhibition of migration on FN respect to FN plus TN. Finally, no difference of metalloprotease (MMP-2, MMP-3, MMP-7, MMP-9) activity was observed between cells plated on FN and on FN plus TN, except for B-MM which showed an increased MMP-7 activity when TN was added to FN. Although TN is not a substrate for movement of MM cell lines, it interacts with FN by modulating differently the migration, according to the different histotype and to the integrin involved, and increasing specific metalloprotease activity.