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

Mind Wandering in Old Age: Lack of Thoughts or Lack of Resources?

Older adults report mind wandering (MW) less than younger adults, a finding opposite of the predictions of inhibitory deficit theory. The present study attempted to reconcile this finding with inhibitory deficit theory through cognitive control theories of MW that posit separate maintenance and initiation mechanisms of MW. The maintenance mechanism was tested in Experiment 1 where participants completed either a visual or auditory 1-back while reporting instances of inner ear (auditory) or inner eye (visual) MW. It was hypothesized that a specific deficit in inner eye MW in older adults would suggest older adults report less MW due to a lack of resources needed to maintain episodes of MW. The initiation mechanism was tested in Experiment 2 where participants completed a sustained attention to response task and an involuntary autobiographical memory task both at a lab and at their homes. It was hypothesized that a smaller gap in reported MW between age groups in a memory cue rich context (their homes) would suggest older adults report less MW because of the lack of memory cues in lab contexts. Neither hypothesis was supported. Older adults were not found to have a specific deficit of inner eye MW, and instead had a pattern suggesting domain specific resources contributed to MW. Additionally, older adults reported less MW when at home, while the gap between age groups remained unchanged. Implications for inhibitory deficit theory, as well as the component process and the control failure X current concerns theories of MW, are discussed

Experiment 1: Lack of Resources

Experiment 1 of the dissertation. Has not been published beyond the dissertation

Experiment 2: Lack of Thoughts

Older adults report less mind-wandering (MW) during tasks of sustained attention than younger adults. The control failure × current concerns account argues that this is due to age differences in how contexts cue personally relevant task-unrelated thoughts. For older adults, the university laboratory contains few reminders of their current concerns and unfinished goals. For younger adults, however, the university laboratory is more directly tied to their current concerns. Therefore, if the context for triggering current concerns is the critical difference between younger and older adults’ reported MW frequencies, then testing the two groups in contexts that equate the salience of self-relevant cues (i.e., their homes) should result in an increase in older but not younger adults’ MW rates. The present study directly compared rates of MW and involuntary autobiographical memories (IAMs) in the home versus in the lab for younger and older adults using a within-subjects manipulation of context. Inconsistent with the control failure × current concerns account, no significant reduction in the age-gap in MW was found. Suggesting a lack of cues rather than an abundance of cues elicits MW, participants in both age groups reported more MW in the lab than at home. The number of IAMs recalled did not differ across contexts but was lower in older than younger adults. These findings suggest that a cognitive rather than an environmental mechanism may be behind the reduction in spontaneous cognition in aging

Efficiënte jaarrondteelt van bramen met LED

In a study conducted by WUR Business Unit Greenhouse Horticulture & Flower Bulbs (WUR) with blackberry, the effects of exposure time and light intensity with LEDs were investigated. The results from this study were compared with measurements by Delphy B.V. on a practical farm with HPS lamps. At WUR, the research was done with the varieties Loch Ness and Von. At an equal daily light sum, long exposure combined with a lower light intensity, increased the production in Von by 4.7% over short exposures with a higher intensity. This result means lower investment costs in LEDs for the blackberry grower. At a higher light intensity under a long exposure, the production increased even more. The grower with HPS used a clearly different climate regime: 2oC higher temperature, 300 ppm higher CO2 level and an 11% higher light sum was achieved. This shortened the development time and increased production