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

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Warning System for European Redmite Using Beta Model

European red mite is a serious problem of apple in Himachal Pradesh. At present more than 80 % orchards have been found infested with European red mite. It sucks cell sap from leaves which resulted into poor quality of fruits. Present studies were undertaken to see the effect of environmental factors e.g. temperature and relative humidity on the buildup of mite population in the apple trees at RHRS, Mashobra. The predicted optimum temperature and relative humidity was calculated by using Beta model is 21.45oC and <85% respectively. Since from the last few years regional observation and experimental database on prediction of pest attack on crop about infection index correspondence to above mentioned environmental parameters was prepared using software Microsoft EXCEL. After that from collected data a mathematical prediction model was developed using the MATLAB as software tool. A generalized form of Beta model was provided to best fit in the data. The value of R2 we observed for eggs and motiles was 82.8 and 84.5 respectively

Oculocutaneous albinism and the oral manifestation in a 14-year-old boy - A case report and review of literature

Albinism consists of a group of genetically inherited autosomal recessive conditions which are typically characterized by a congenital reduction or absence in melanin pigment biosynthesis which gives the natural color in the skin, iris of the eyes, and hair. A person with albinism may have one or many of the following symptoms: absence of color in the hair, skin, or iris of the eye, lighter than normal skin and hair, patchy, missing skin color, crossed eyes (strabismus), light sensitivity (photophobia), rapid eye movements (nystagmus), vision problems, or functional blindness, severe gingivitis, oral mucosal ulceration, and periodontal disease. A dentist can play a significant role in successfully treating albino patients if he/she has basic knowledge of the symptoms of albinism. We present a case report of a 14-year-old child suffering from oculocutaneous albinism who was reported to the Department of Periodontology, Himachal Pradesh Government Dental College and Hospital, Shimla, Himachal Pradesh, with a chief complaint of bleeding gums and oral malodor

Disease Forecasting and Pest Management for Indian Apple: An Application of ICT

Apple is one of the most widely cultivated fruit crops in region of northern hilly area of Jammu & Kashmir and Himachal Pradesh. In the present study a system is suggested and under development by authors using the information and communication technology (ICT) which predict the growth of various disease in Apple fruit like Apple scab, Marssonina blotch, Red mite pest etc. and communicate to farmers on their mobile about pre information of severity of disease so that they can easily handle the risk by pest management. This system provides solution to mitigate the disease risk. As an ICT tools different kind of wireless sensors, Data acquisition Card, computer, network protocol (TCP/IP), GPRS, GSM mobile communication module and web interface protocol were used to design the complete forecasting system. Growth of apple disease and pests are highly dependent on various environmental parameters like temperature, Relative humidity (RH), wind velocity/direction, and leaf wetness duration that were measured by particular sensors and using prediction model the infection of index was calculated which tells about severity of risk and this information are sent to farmers and also to the server located at far away from field using GPRS (General packet radio service). This ICT application consist both hardware and software phase to extract the information about the risk and this processed information is shared on web page which can be easily accessible from every corner of the world