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

Seismic evidence for an Iceland thermo-chemical plume in the Earth's lowermost mantle

International audienc

Sample Expansion and Classification Model of Maize Leaf Diseases Based on the Self-Attention CycleGAN

In order to address the limited scale and insufficient diversity of research datasets for maize leaf diseases, this study proposes a maize disease image generation algorithm based on the cycle generative adversarial network (CycleGAN). With the disease image transfer method, healthy maize images can be transformed into diseased crop images. To improve the accuracy of the generated data, the category activation mapping attention mechanism is integrated into the original CycleGAN generator and discriminator, and a feature recombination loss function is constructed in the discriminator. In addition, the minimum absolute error is used to calculate the differences between the hidden layer feature representations, and backpropagation is employed to enhance the contour information of the generated images. To demonstrate the effectiveness of this method, the improved CycleGAN algorithm is used to transform healthy maize leaf images. Evaluation metrics, such as peak signal-to-noise ratio (PSNR), structural similarity (SSIM), Fréchet inception distance (FID), and grayscale histogram can prove that the obtained maize leaf disease images perform better in terms of background and detail preservation. Furthermore, using this method, the original CycleGAN method, and the Pix2Pix method, the dataset is expanded, and a recognition network is used to perform classification tasks on different datasets. The dataset generated by this method achieves the best performance in the classification tasks, with an average accuracy rate of over 91%. These experiments indicate the feasibility of this model in generating high-quality maize disease leaf images. It not only addresses the limitation of existing maize disease datasets but also improves the accuracy of maize disease recognition in small-sample maize leaf disease classification tasks

Efficacy of Stereotactic Body Radiotherapy for Recurrent or Residual Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization

Aim. To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) for patients with recurrent or residual hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). Methods. Between June 2008 and July 2015, thirty-three patients with HCC were treated by SBRT. There were 63 lesions in 33 patients. A total dose of 39–45 Gy/3–5 fractions was delivered to the 70–80% isodose line. Results. Objective response rate (CR + PR) was 84.8% at 6 months. The overall survival rate was 87.9%, 75.8%, 57.6%, and 45.5% at 6, 12, 18, and 24 months, respectively. Median overall survival was 19 months. At 3 months, AFP decreased by more than 75% in 51.5% of patients (17/33). Overall survival was significantly different (P<0.001) between the group of patients for whom AFP decreased more than 75% and the group for whom AFP decreased by less than 75%. The AFP-negative rate was 48.5% (16/33) after 6 months. Eight patients (24.2%) had grade 1-2 transient fatigue, and 11 patients (33.3%) had grade 1-2 gastrointestinal reactions within 1 month. Conclusion. SBRT is a promising noninvasive and palliative treatment with acceptable toxicity for recurrent or residual HCC after TACE