Developing the Duffy Defect: Identifying Which Government Workers are Constitutionally Required to Be Appointed

In 2007, Professor John Duffy wrote a brief article questioning whether administrative patent judges are constitutional officers and therefore subject to the Appointments Clause. A litigant latched onto the argument and challenged the validity of eight years of Board of Patent Appeals and Interferences determinations. Congress enacted a patch to provide for the appointment of patent judges, but the Duffy Defect did not stop there. Other scholars have questioned the constitutionality of various government actors from Bankruptcy Judges to the Pay Czar. The United States Tax Court dealt with a recent Appointments Clause challenge when a taxpayer questioned whether Internal Revenue Service (IRS) Appeals personnel who perform Collection Due Process hearings or their managers must be appointed Given the broad powers of the current administrative state, these questions are bound to become common challenges to agency action and have strong potential to halt the federal government unless legislative action is taken proactively. The Constitution provides little guidance on the characteristics that define an officer, noting only that an office must be established by Law. The Supreme Court has added that an officer is one who exercises significant authority pursuant to the laws of the United States. This Article attempts to define those phrases in a robust manner that preserves the separation of powers and political accountability. It first reviews the Appointments Clause, its history and purposes, and relevant legal precedent. To lend the reader context, it summarizes the current Collection Due Process procedures and describes the power the IRS Appeals Office holds. The Article analyzes the Tax Court\u27s holding, concluding that the Tax Court offers Congress a blueprint to avoid the Appointments Clause. The Article suggests an alternative framework for evaluating officer status and determines that IRS personnel should be appointed. The Article concludes with a consideration of the effects of such a holding in the context of our current government structure and political environment

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