Stimulating a key metabolic pathway in T cells can make them work more effectively against tumors when combined with immune checkpoint inhibitor therapy, according to a preclinical study led by researchers at Weill Cornell Medicine. The findings suggest a potential strategy for enhancing the potency of anticancer immunotherapies. In the study , which appears Sept.
26 in Nature Immunology , the researchers discovered that activating a metabolic pathway called the pentose phosphate pathway makes antitumor CD8 T cells more likely to stay in an immature, stem-like, "precursor" state. They showed that combining this metabolic reprogramming of T cells with a standard anticancer immune checkpoint inhibitor treatment leads to big improvements in tumor control in animal models and in tumor "organoids" grown from human tumor samples. "Our hope is that we can use this new metabolic reprogramming strategy to significantly boost patients' response rates to immune checkpoint inhibitor therapies," said study senior author Dr.
Vivek Mittal, the Ford-Isom Research Professor of Cardiothoracic Surgery at Weill Cornell Medicine. The study's lead author was Dr. Geoffrey Markowitz, a postdoctoral research associate in the Mittal laboratory.
T cells and other immune cells , when active, eventually start to express immune-suppressing checkpoint proteins such as PD-1, which are thought to have evolved to keep immune responses from running out of control. Within the past decade, immunotherapies that b.