Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact

BACKGROUND: Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value. METHODS: Tumour-infiltrating lymphocytes (CD4, CD8, Foxp3), mast cells (MCs) (tryptase and chymase), microvessel count (MVC) and VEGF were determined by immunohistochemistry in two series of MPM patients: 60 patients treated with intra-pleural preoperative IL-2 and 33 patients untreated. RESULTS: Tryptase MCs, and CD8 and Foxp3 lymphocytes were significantly increased in the IL-2-treated group, whereas MVC was significantly lower in the same group. Moreover, in the IL-2-treated group, greater tryptase + MCs and greater Foxp3 lymphocytes were associated with improved and poorer clinical outcomes, respectively. Notably, when these two immunological parameters were combined, they predicted outcomes more effectively. CONCLUSIONS: This study showed that IL-2 treatment leads to a significant increase of immunological parameters, concomitantly with a reduction in vasculature, providing new insight into the cancer mechanisms mediated by IL-2. Moreover, these results suggest that tryptase-positive MCs and Foxp3 + lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression. British Journal of Cancer (2009) 101, 1869-1875. doi:10.1038/sj.bjc.6605438 www.bjcancer.com (C) 2009 Cancer Research U

The importance of indirect cues for white-browed sparrow-weaver (Plocepasser mahali) risk assessment

Both direct cues that provide information about the actual presence of a predator and indirect environmental cues that provide information about the probability of encountering a predator may be used by animals assessing predation risk, but relatively few studies manipulate both simultaneously to study their relative importance. We conducted two experiments to study the foraging decisions of white-browed sparrow-weavers (Plocepasser mahali). The first experiment manipulated both direct and indirect cues in a feeding array by simultaneously placing feeding stations at different distances from humans (to manipulate direct risk) and from protective cover (to manipulate indirect risk). Weaver foraging was influenced more by indirect risk than by direct risk. The second experiment aimed to determine if weaver’s indirect risk assessment was sensitive to variation in benefits. We set two feeding stations at different distances from cover but the same distance from the human observers and systematically increased the amount of food at the station farther from cover. Weavers far from cover initially foraged at higher rates than those close to cover, but the addition of food reduced the foraging rate. Together, our results illustrate that weaver foraging decisions are sensitive to variation in risk and that indirect cues are relatively more important than direct cues