How Decades of NCI Support Led to Groundbreaking Discoveries: The Story of Immune Checkpoint Inhibitors
Research news (July 21, 2026) from an NCI “Your NCI” blog post reviews how decades of NIH/NCI-funded basic and translational science contributed to the development of immune checkpoint inhibitors. The article outlines discovery of immune “brakes” CTLA-4 and PD-1 and how blocking these pathways can restore antitumor T-cell activity. It notes that checkpoint inhibitors such as pembrolizumab (Keytruda) now have more than 40 approved treatment indications across multiple cancers.
Research news (NCI blog) — July 21, 2026
A National Cancer Institute (NCI) “Your NCI” blog post describes how sustained NIH/NCI support since the late 1970s helped enable the scientific and clinical development of immune checkpoint inhibitors.
The article explains the checkpoint concept as molecular “brakes” that restrain T-cell responses to prevent damage to healthy tissue, and how tumors can exploit these pathways to evade immune attack. Checkpoint inhibitors block these suppressive signals, potentially allowing T cells to recognize and destroy cancer cells.
Key scientific milestones cited include:
- 1990s work led by James P. Allison, PhD, identifying CTLA-4 as an immune inhibitory checkpoint.
- Tasuku Honjo, MD, PhD, and colleagues’ discovery of PD-1 as a distinct immune checkpoint protein.
- Subsequent studies showing that blocking CTLA-4 or PD-1 pathways could restore antitumor immunity.
The post also highlights translation into clinical testing, noting that ipilimumab (Yervoy; CTLA-4) entered clinical trials starting around 2000, and that pembrolizumab (Keytruda; PD-1) was first administered to patients with advanced melanoma in 2011. It references the KEYNOTE-001 trial, reporting that NCI-supported investigators (including Antoni Ribas, MD, PhD) observed dramatic tumor shrinkage in advanced melanoma.
The article states that pembrolizumab is approved for more than 40 treatment indications across a wide variety of cancers.