31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effectiveness of differing trap types for the detection of emerald ash borer (Coleoptera: Buprestidae)

The early detection of populations of a forest pest is important to begin initial control efforts, minimizing the risk of further spread and impact. Emerald ash borer (Agrilus planipennis Fairmaire) is an introduced pestiferous insect of ash (Fraxinus spp. L.) in North America. The effectiveness of trapping techniques, including girdled trap trees with sticky bands and purple prism traps, was tested in areas with low- and high-density populations of emerald ash borer. At both densities, large girdled trap trees (\u3e 30cm diameter at breast height [dbh], 1.37 m in height) captured a higher rate of adult beetles per day than smaller trees. However, the odds of detecting emerald ash borer increased as the dbh of the tree increased by 1 cm for trap trees 15-25 cm dbh. Ash species used for the traps differed in the number of larvae per cubic centimeter ofphloem. Emerald ash borer larvae were more likely to be detected below, compared with above, the crown base of the trap tree. While larval densities within a trap tree were related to the species of ash, adult capture rates were not. These results provide support for focusing state and regional detection programs on the detection of emerald ash borer adults. If bark peeling for larvae is incorporated into these programs, peeling efforts focused below the crown base may increase likelihood of identifying new infestations while reducing labor costs. Associating traps with larger trees (̃25 cm dbh) may increase the odds of detecting low-density populations of emerald ash borer, possibly reducing the time between infestation establishment and implementing management strategies. © 2009 Entonsological Society of America

Improving the efficiency of Lepidopteran pest detection and surveillance: constraints and opportunities for multiple-species trapping

Surveillance using attractants for invasive species can allow early detection of new incursions and provide decision support to response programs. Simultaneous trapping for multiple species, by baiting traps with several lures, is expected to increase the number of species that can be targeted in surveillance programs and improve the cost-effectiveness without affecting surveillance coverage. We tested this hypothesis by choosing four potential forest and urban lepidopteran pest species that are present in Europe but not yet in New Zealand and many other countries. We deployed traps in central and southern Europe with single lures or all possible species combinations (up to four lures per trap). There was only limited interference, apparently due to trap saturation, but no evidence for interspecific repellency among lures for gypsy moth, Lymantria dispar, fall webworm, Hyphantria cunea, pine processionary moth, Thaumetopoea pityocampa, and pine shoot moth, Rhyacionia buoliana. To assess what factors may be important in species compatibility/suitability for multiple-species trapping, we combined our results with those of previous studies conducted by the United States Department of Agriculture. For 75 combinations of pheromones, tested singly or in combination, 19 % showed no effect on trap catch for any of the species tested. In the other cases, either one or both species showed a reduction in trap catch. However, few lure combinations caused complete or nearly complete suppression. For most combinations, catches were still sufficiently high for detection purposes. Species from the same superfamily exhibited more interference than more distantly related species. Together, these results suggest that there are opportunities to improve the range of exotic pests under surveillance, at little additional cost, by multiple-species trapping for which compatibility has been demonstrated

Data from: Genetic structure, admixture, and invasion success in a Holarctic defoliator, the gypsy moth (Lymantria dispar, Lepidoptera: Erebidae)

Characterizing the current population structure of potentially invasive species provides a critical context for identifying source populations and for understanding why invasions are successful. Non-native populations inevitably lose genetic diversity during initial colonization events, but subsequent admixture among independently introduced lineages may increase both genetic variation and adaptive potential. Here we characterize the population structure of the gypsy moth (Lymantria dispar Linnaeus), one of the world's most destructive forest pests. Native to Eurasia and recently introduced to North America, the current distribution of gypsy moth includes forests throughout the temperate region of the northern hemisphere. Analyses of microsatellite loci and mitochondrial DNA sequences for 1738 individuals identified four genetic clusters within L. dispar. Three of these clusters correspond to the three named subspecies; North American populations represent a distinct fourth cluster, presumably a consequence of the population bottleneck and allele frequency change that accompanied introduction. We find no evidence that admixture has been an important catalyst of the successful invasion and range expansion in North America. However, we do find evidence of ongoing hybridization between subspecies and increased genetic variation in gypsy moth populations from Eastern Asia, populations that now pose a threat of further human-mediated introductions. Finally, we show that current patterns of variation can be explained in terms of climate and habitat changes during the Pleistocene, a time when temperate forests expanded and contracted. Deeply diverged matrilines in Europe imply that gypsy moths have been there for a long time and are not recent arrivals from Asia