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

Perspectives from the 2022 cohort of the American Chemical Society Summer School on Green Chemistry & Sustainable Energy

The field of chemistry is uniquely equipped to solve many current and impending global challenges; however, minimizing potential negative impacts on the environment, society, and the economy requires a holistic approach to developing new processes and chemicals. For this reason, there is an urgent need to incorporate green chemistry and systems thinking into chemistry-based disciplines so that the most sustainable, least toxic, and least resource-intensive research directions and methods are prioritized. The next generation of researchers and instructors is poised to implement these approaches; however, most graduate curricula do not include coursework on green chemistry and systems thinking. Every year, the American Chemical Society Green Chemistry Institute hosts the Summer School on Green Chemistry & Sustainable Energy for early career researchers to learn about green chemistry and systems thinking approaches for tackling sustainability goals. In this Perspective, 2022 summer school participants highlight sustainability challenges in their own work that can be addressed using the skills and knowledge acquired at the summer school, including in carbon capture, organic pharmaceutical synthesis, nanomaterial synthesis, catalysis, and other areas. In addition, how green chemistry can meet practical needs in industry settings and be infused in education and government policy is discussed.Fil: Saraf, Mohit. Drexel University; Estados UnidosFil: Roy, Monika A.. University Of Massachusetts Lowell; Estados UnidosFil: Yarur Villanueva, Francisco. University of Toronto; CanadáFil: Kundu, Anirban. Université Mcgill; CanadáFil: Tran, Hung-Vu. University Of Houston; Estados UnidosFil: Ghosh, Moumita. Indiana University; Estados UnidosFil: Ezenwa, Sopuruchukwu. Purdue University; Estados UnidosFil: Gastelu, Gabriela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Prebihalo, Emily A.. University of Minnesota; Estados UnidosFil: Cala Gómez, Luis Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Cleary, Scott R.. Colorado School Of Mines; Estados UnidosFil: Devineni, Geetesh. The George Washington University; Estados UnidosFil: Lee, Gahyun Annie. The Fu Foundation School Of Engineering And Applied Science; Estados UnidosFil: Umenweke, Great C.. University of Kentucky; Estados UnidosFil: Koby, Ross F.. University of Minnesota; Estados UnidosFil: Nixon, Rachel. University of Illinois. Urbana - Champaign; Estados UnidosFil: Voutchkova, Adelina. American Chemical Society. Office of Sustainability; Estados Unidos. The George Washington University; Estados UnidosFil: Moores, Audrey. Université Mcgill; Canad