The story behind the development of immune checkpoint inhibitors, fulfilling the promise of cancer immunotherapy

Partners in research as well as marriage, Arlene Sharpe, MD ’82, PhD ’81, Kolokotrones University Professor and chair of immunology at HMS, and Gordon Freeman, PhD ’79, professor of medicine at Dana-Farber and HMS, have collaborated for decades to understand how cancer evades the immune system. In the early 2000s, they discovered that certain malignant tumors exploit the immune system’s PD-1/PD-L1 signaling pathway to avoid detection and that blocking these molecules boosts T-cell activity against cancer.

Building on their research, Ira Mellman, PhD, then VP of cancer immunology at Genentech, developed anti-PD-1 and anti-PD-L1 therapies—including Tecentriq—which gained FDA approval and transformed cancer care. Such immune checkpoint inhibitors have dramatically improved patient outcomes; in recent studies, half of those with advanced melanoma have survived beyond 10 years. As Dr. Mellman notes, “None of this would have ever happened were it not for basic science.”