Mutants. Oncogene. 2007; 26(15), 2226-2242. six. McKenzie, J A, Mbofung, R M ., Malu, S, Zhang, M, Ashkin, E, Devi, S, Xu, C. The Impact of Topoisomerase I Inhibitors on the Efficacy of T-Cell-Based Cancer Immunotherapy. J Natl Cancer Inst. 2018;110(7):777-786.P556 STAT3-related cytokines drive IR-specific immune suppression of effector, memory and na e, peripheral blood CD8+ T cells in cancer BACE2 Gene ID sufferers Ashwin Somasundaram, MD, Dario A. Vignali, PhD, Anthony Cillo, PhD, James Herman, John Kirkwood, MD, Robert Ferris, MD, PhD, Tullia Bruno, PhD University of Pittsburgh, Pittsburgh, PA, USA Correspondence: Dario A. Vignali ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P556 Background Cancer sufferers that usually do not respond to PD1 blockade have elevated inhibitory receptor (IR) expression in peripheral blood lymphocytes (PBL) and improved cytokine concentrations within the plasma. Cancer individuals off therapy and with typical white blood cell counts are often at greater danger for infections, immune dysregulation, progressive illness or reactivation of viral infections. Nevertheless, the exact mechanism of this systemic immunosuppression in cancer individuals isP555 A function for mutant p53 in mediating T cell immune evasion in pancreatic adenocarcinoma along with other solid tumors Deborah Silverman, BS, Emily Ashkin, Simone Punt, PhD, Minying Zhang, Leila Williams, MSc, Anil Korkut, Jason Roszik, PhD, Anirban Maitra, MBBS, Patrick Hwu, MD MD Anderson Cancer Center, Houston, TX, USA Correspondence: Deborah Silverman ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):PJournal for ImmunoTherapy of Cancer 2018, 6(Suppl 1):Page 297 ofnot completely understood. We performed flow cytometric assays to assess both phenotype and function of peripheral CD8+ T cells in cancer patient samples and wholesome donor controls. We hypothesize that cancer sufferers could have systemic immune suppression by way of cytokine-driven IR expression in all CD8+ T cells subsets, like na e cells. Procedures PBL had been obtained from healthful donors and treatment-na e NSCLC, HNSCC, and melanoma patients. IR (i.e. LAG3, PD1, CTLA4, etc) expression was assessed on CD8+ T cells, CD4+ T cells, and regulatory T cells. Cytokine concentrations had been compared by Luminex amongst HD1 Purity & Documentation plasma from healthy donors and plasma from cancer individuals with higher and low IR expression on peripheral CD8+ T cells. Autologous micro-stimulation assays had been performed on peripheral CD8+ or CD4 + T cells with antigen presenting cells plus or minus IR blockade. Results CD8+ T cells, such as CD45RA+CCR7+CD62L+CD8+ T cells, from cancer patient PBL include elevated total LAG3 expression which correlated with stage and elevated expression of other IRs. Further, CD8 + T cells from these individuals had decreased proliferation, which was rescued using the addition of anti-LAG3 or anti-PD1. Plasma from these sufferers had considerably elevated levels of cytokines which can signal through STAT3 (i.e. IL-6, IL-8, IL-9), which have been independently located to raise total IR expression in healthy donor, na e CD8+ T cells. Conclusions The present understanding of PD1 blockade resistance has been restricted for the tumor microenvironment (TME) and our findings help the growing physique of literature that tumor-related systemic immune suppression is actually a potent mechanism of cancer progression. Sufferers with cancer have systemic elevations of cytokines that signal via STAT3 top to enhanced IR expression in na e, peri.