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

Image-guided marker placement in liver tumors for stereotactic radiotherapy: technique and safety

PURPOSE: To evaluate the technique and safety of percutaneous radiopaque gold marker placement in the liver before external stereotactic radiotherapy for intrahepatic tumors. MATERIALS AND METHODS: Thirteen patients were included in this study. One gold marker per patient was placed using a computed tomographic fluoroscopy procedure. Follow-up was carried out with a multislice computed tomographic scan. RESULTS: A marker was placed in the center (n = 6) or in the periphery (n = 7) of the target lesion. No immediate complications were noted. Long-term follow-up showed changes in coil position relative to liver anatomy in 4 cases; all 4 markers were placed in the center of the target lesion. No other long-term complications were seen. CONCLUSIONS: Radiopaque markers can be placed safely in liver lesions before external stereotactic radiotherapy. However, marker displacement can occur early, thereby compromising the precision of the planned treatment. The decreased size of the tumor as a response to therapy was responsible for late migration in this small series

Enterobius vermicularis Infection with tuboovarian abscess and peritonitis occurring during pregnancy

Background: Extraintestinal Enterobius vermicularis infections are rare but may occasionally affect the female genital tract. Although mostly asymptomatic or causing minor clinical problems, they may lead to severe infectious complications. Methods: Case report and review of the pertinent English language literature. Results: A 31-year-old, 30-week-pregnant female was admitted with a clinical suspicion of appendicitis. At surgery, the appendix appeared normal, but generalized peritonitis of unclear origin was present. Eggs of Enterobius vermicularis were found upon microbiological and pathological examination. Because of persisting infectious disease, the patient underwent an elective caesarean section, and at that time the diagnosis of a right tuboovarian abscess was made, and salpingo-oophorectomy was performed. The pathology report confirmed the diagnosis of an E. vermicularis salpingo-oophoritis. Conclusion: This case was extraordinary because of a combination of tuboovarian abscess and generalized peritonitis with E. vermicularis infection occurring during late pregnancy. Ectopic enterobiasis should be considered in the differential diagnosis of pelvic infections of gynecological origin