Prologue: The Elimination of Biochemical and Immunological Barriers in the Tumor Microenvironment to Improve Cancer Immunotherapy

Monday, October 17, 2022

8:30 AM – 9:00 AM ET

Location:255

Prologue Speaker(s)

Stephen Hatfield, PhD

Assistant Professor
Northeastern University

Promising results from the first in-human clinical studies using antagonists of the A2A Adenosine Receptor (A2AR) for treatment of renal cell carcinoma highlight two decades of research into the hypoxia-A2-adenosinergic pathway. Positive responses have been observed in patients who previously progressed on anti-PD1/PD-L1 therapy, emphasizing the clinical importance of targeting biochemical and immunological negative regulators during cancer immunotherapies. The combination therapy of A2AR blockade and anti-PD1 therapy has improved clinical outcomes and resulted in immune-mediated tumor regression in patients with PD1-resistant refractory renal cell carcinoma, metastatic castration-resistant prostate cancer, and pancreatic cancers. The attractiveness of this strategy is further supported by the availability and established safety profile of drugs targeting the A2AR pathway.

Learning Objectives:

Detailed overview and current update of the fundamental molecular mechanisms of the hypoxia-adenosinergic axis of immunosuppression.
Describe the recent clinical developments in targeting this pathway in patients with aggressive tumors resistant to immune checkpoint blockade.
Discuss recent preclinical data and future clinical promise of the use of inhibitors of A2AR to improve cell-based cancer therapies
Targeting of tumor hypoxia and HIF-1α-mediated suppression in the tumor microenvironment