“I was saved by a fabulous treatment and great doctors, and a real miracle [drug] called PD-1 therapy. I went into trials for that PD-1, and it has been one of the great medicines. I now have no tumors," Dallas Cowboys owner Jerry Jones recounts in his interview with the Dallas Morning News.

Jones’s battle with cancer was revealed in the upcoming eight-part Dallas Cowboys series on Netflix, where he referenced undergoing cancer treatments “about a dozen years ago.”

He was diagnosed with melanoma in June 2010 and received treatment at the MD Anderson Cancer Center in Houston. Over the decade following his diagnosis, he underwent two lung surgeries and two lymph node surgeries due to the cancer spreading. After sharing his battle with cancer publicly, Jones credits an experimental drug therapy called PD-1 (Programmed Cell Death Protein 1) with saving his life.

So how does this immunotherapy work, and how does blocking the PD-1 protein help eliminate cancer cells in Jones?

What Is PD-1 Therapy?

In 1992, PD-1 (programmed cell death protein 1) was identified by Tasuku Honjo and colleagues at Kyoto University as a gene thought to be involved in apoptosis (programmed cell death). It was later discovered that PD-1 is not directly tied to cell death, but instead acts as an immune checkpoint, a “brake” that slows down T-cells, a type of immune cell.

Cancer cells take advantage of this braking system to escape the body’s defenses. PD-1 functions as a receptor (the lock) on immune cells, while PD-L1, its ligand (the key), is expressed on tumor cells and other types of cells. So when PD-L1 on tumor cells binds to PD-1 on immune cells, it effectively “locks the door,” shutting the immune system out and preventing it from attacking the cancer.

Under normal conditions, PD-1 is critical for protecting the body by turning off immune cells to prevent autoimmune disease, reducing harmful inflammation, and restoring the function of exhausted immune cells. Cancer, however, hijacks this protective mechanism to fuel its own growth and spread.

PD-1 is one of several immune checkpoint proteins that help cancer evade the immune system. Other well-studied checkpoint proteins, CTLA-4 and LAG-3, also play a critical role in this process.

How Does Blocking PD-1 in Cancer Work?

In 2002, Tasuku Honjo and colleagues first studied the role of PD-1/PD-L1 in cancer. Using mice, they found that blocking PD-L1 with drugs reduced myeloma growth. They also discovered that mice lacking PD-1 had severely limited melanoma spread from the spleen to the liver. These findings provided early evidence that blocking PD-1 or PD-L1 could be an effective strategy for treating cancer.

Twelve years later, in 2014, the U.S. Food and Drug Administration (FDA) approved the first PD-1 inhibitor, pembrolizumab (Keytruda), for patients with metastatic melanoma who had previously received ipilimumab, including those with BRAF V600 mutation melanoma. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor, preventing its interaction with PD-L1. This reactivates T-cells, allowing them to attack cancer cells.

Schematic illustrating the mechanism of the PD1/PDL1 system in cancer. Image obtained from Wikimedia Commons.

Following its success in melanoma, several other PD-1 inhibitors have been investigated and approved for a range of cancers, including nivolumab, cemiplimab, dostarlimab, atezolizumab, and avelumab. These drugs are now used in non-small cell lung cancer, renal cell carcinoma, endometrial cancer, Merkel cell carcinoma, cutaneous squamous cell carcinoma, and Hodgkin lymphoma.

Despite this progress, challenges remain in treating melanoma due to treatment resistance. Researchers continue to study new strategies, including different drug combinations and the development of more effective PD-1 inhibitors.

While specifics about the trial Jones participated in are not publicly available, several ongoing clinical trials are assessing new PD-1–based therapies for advanced melanoma. For instance, one trial is testing EIK1001, an immune cell–activating drug, in combination with pembrolizumab. Another Phase 2 trial investigated the combination of BO-112 with Pembrolizumab for melanoma patients resistant to PD-1 inhibitors. These ongoing trials build on the success of existing PD-1 and other checkpoint inhibitors, aiming to overcome treatment resistance and stimulate stronger responses through combination therapies.

How Dallas Cowboys Stories Spotlight Progress in Cancer Treatment

Dubbed the “America’s Team,” the Dallas Cowboys’ iconic wins and cultural impact extend far beyond the sports world. After Jones’s public disclosure of his battle with cancer, current Cowboys coach Brian Schottenheimer revealed that he was diagnosed with thyroid cancer at age 28. He underwent surgery to remove his thyroid and 17 lymph nodes. “You hear that word ‘cancer’ and it scares the hell out of you,” Schottenheimer said. “I’m glad that Jerry shared it, just because I think it gives people hope. It gives people the strength to say, ‘Hey, you can beat this, you can do that.’”

Although melanoma accounts for only 1% of all skin cancer cases, it causes more than 80% of skin cancer deaths. According to the American Cancer Society (ACS), only about 35% of patients with advanced melanoma survive five years after diagnosis. However, that number has been steadily improving as new therapies emerge. “There is some reassurance in knowing that significant advances have been made in treating skin cancers, especially when they become more advanced or aggressive, like melanoma or Merkel cell carcinoma. We can feel confident in the treatment options available today, even if a skin cancer diagnosis does occur,” Dr. Shailender Bhatia, the director of the melanoma and renal cancer team at Fred Hutchinson Cancer Center, said.

Jones’s recovery is a remarkable testament to the power of medical innovation and the importance of research. Reflecting on his cancer journey and expressing gratitude for scientific discovery, Jones shared, “You don’t like to think about your mortality, but I was so fortunate to have some great people that sent me in the right direction. I got to be part of a trial that was propitious. It really worked.”

Works Discussed

• Ishida, Y. (2020). PD-1: Its discovery, involvement in cancer immunotherapy, and beyond. Cells, 9(6), 1376. https://doi.org/10.3390/cells9061376
• Townsend, B. (2025, August 13). 'I've been blessed': Cowboys' Jerry Jones shares more details on overcoming Stage 4 cancer. The Dallas Morning News. https://www.dallasnews.com/sports/cowboys/2025/08/13/dallas-cowboys-jerry-jones-cancer-stage-4-four-melanoma-reveal-nfl/
• Gong, C., & Liu, G. (2021). A snapshot of the PD-1/PD-L1 pathway. Journal of Cancer, 12(9), 2735-2746. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040720/
• Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences of the United States of America, 99(19), 12293–12297. https://doi.org/10.1073/pnas.192461099
• American Cancer Society. (2025, January 16). Survival rates for melanoma skin cancer, by stage. https://www.cancer.org/cancer/types/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage.html
• Yarish, T. (2025, August 13). Brian Schottenheimer reveals he was diagnosed with thyroid cancer at 28. DallasCowboys.com. https://www.dallascowboys.com/news/brian-schottenheimer-reveals-he-was-diagnosed-with-thyroid-cancer-at-28