Dallas Cowboys owner Jerry Jones revealed this week that he battled stage 4 melanoma for over a decade.
Throughout his treatment, he had 2 surgeries and participated in a clinical trial at MD Anderson that involved PD‑1 immunotherapy, an experimental treatment that helps the immune system recognize and attack cancer cells. Today, Jones says he is tumor‑free, crediting PD‑1 therapy for saving his life.
What is PD1-therapy?
PD-1 stands for Programmed Death-1, which is a receptor found on the surface of certain immune cells (mainly T cells). Its normal job is to act like a “brake” on the immune system, helping prevent overactivation that could damage healthy tissues.
Some cancer cells produce a protein called PD-L1 (Programmed Death-Ligand 1), which binds to PD-1 on T cells and essentially shuts them off. This lets the tumor cells “hide” from the immune system.
PD-1 therapy refers to drugs called PD-1 inhibitors (or “immune checkpoint inhibitors”) that block this interaction. These therapies prevent PD-1 from binding to PD-L1, releasing the brake on T cells, allowing them to recognize and destroy cancer cells more effectively. Examples of PD-1–blocking drugs include:
- Nivolumab (Opdivo)
- Pembrolizumab (Keytruda)
- Cemiplimab (Libtayo)
Tumor cells can produce PD-L1, which binds to the PD-1 receptor on T cells and dampens the immune attack. Drugs that block PD-1 or PD-L1 release this brake, allowing T cells to destroy the tumor.
A few things to know about melanoma:
Melanoma develops from melanocytes, the pigment-producing cells in the skin. It’s known for its ability to spread quickly once it penetrates deeper layers of the skin and for being biologically adaptable, meaning it can survive in many different environments in the body.
Historically, traditional chemotherapy has had limited success against melanoma. Response rates are generally low, and remissions tend to be short-lived. This is partly because melanoma cells have a high degree of chemoresistance and can pump chemotherapy drugs out of the cell, making them less sensitive to treatments.
Melanoma is considered one of the most immunogenic cancers. It tends to carry a high number of DNA mutations, which produce abnormal proteins on the tumor surface. These abnormal proteins act as “flags” the immune system can recognize.
In theory, the immune system should attack these cells, but many melanomas engage the PD-1/PD-L1 pathway to suppress the T cells that would normally destroy them. Clinical trials have shown that PD-1 inhibitors can produce long-lasting remissions in some patients, even with advanced or metastatic disease, something rarely seen with chemotherapy alone.
The success seen with PD-1 immunotherapy is encouraging! However, it does reflect a larger shift in oncology.
Immunotherapy is now receiving a lion’s share of research investment and development focus. The global cancer immunotherapy market was valued at approximately $123 billion in 2024 and is projected to nearly triple by 2034.
It’s important to recognize that at its core, immunotherapy follows the same central idea as chemotherapy, surgery, or radiation: remove or kill the tumor. That can be an important and necessary step, reducing tumor burden can relieve symptoms, lower inflammatory stress, and improve the effectiveness of other treatments, but it doesn’t address why the tumor developed in the first place. Like with all cancers, we have to look at the terrain that allowed it to grow.
Some terrain imbalances in melanoma:
- Hormones. Research shows a direct correlation between excess estrogen and melanoma. Elevated levels can create a microenvironment that allows melanoma to develop, proliferate, and metastasize. Melanoma cells typically express estrogen receptors. One study found a 53% increase in melanoma risk in women on HRT taking estradiol without progesterone (PMID: 35028367).
- Diet. Like all cancers, diet plays a large role in skin cancer. A diet deficient in nutrients including vitamin A, C, D, and E, and minerals like zinc and selenium, can increase the risk, especially because they are important for mitigating cell damage (PMID: 25995818).
- Chemical exposure. Exposure to certain chemicals, such as those in pesticides, industrial pollutants, or even skincare products, can increase the risk of skin cancer. Benzenes and petroleum products are frequently linked to skin cancer and, incidentally, often used in sunscreens, creams, and lotions (PMID: 28692192).
- Polyunsaturated fats (PUFAs). Ingesting or topically applying these fats can damage cells. They are highly prone to oxidation, especially when exposed to heat. High concentrations of PUFAs can accumulate in the hypodermis—the fat layer beneath the skin. When exposed to UVB light, these fats oxidize and can cause inflammation. This can induce DNA damage and increase the potential for cancer (PMID: 29636341) .
- Inconsistent sun exposure. This is also another major risk factor. Getting large doses at one time without consistently exposing the skin can increase the likelihood of burns and cell damage.
There are usually multiple factors at play, so effective treatment means addressing each of them. It’s all about the terrain of the body.