Dr. Allison showed that the molecule CTLA-4 is an inhibitory receptor that serves as a checkpoint to limit the expansion of T cells and pioneered the concept of blocking CTLA-4 to enhance immune responses to tumor cells. He developed an antagonistic anti-CTLA-4 antibody and based on elegant laboratory experiments, he convinced pharmaceutical companies and clinicians to conduct trials with anti-CTLA-4. Clinical trials in patients with metastatic melanoma demonstrated a survival benefit, which led to the approval of anti-CTLA-4 by the US Food and Drug Administration in March 2011. Anti-CTLA-4 represents a rationally designed mechanistic immunotherapy agent that is now a standard of care for the treatment of metastatic melanoma. This seminal work led to the identification of another checkpoint, PD-1, which also enhances anti-tumor responses and has been approved by the FDA for the treatment of melanoma and several other types of cancer. Thus, Allison’s work opened a new field termed “immune checkpoint therapy” and other agents are being developed to target additional inhibitory or co-stimulatory T-cell molecules. Dr. Allison translated his research work on T cells into a breakthrough therapeutic modality that has transformed cancer treatment and is saving lives worldwide.